Di- and tri-olefinic thiolesters

ABSTRACT

Aliphatic hydrocarbon tri-olefinic and aliphatic substituted diolefinic acids, esters, thiolesters and derivatives thereof, intermediates therefor, syntheses thereof, and the control of insects.

United States Patent 1191 [111 3,882,156

Henrick et a1. May 6, 1975 1 i DI- AND TRI-OLEFINIC THIOLESTERS [51] Int. Cl. C07c 153/01 [75] Inventors, Clive A. "enrick; John B Sidda", [58] Fleld of Search 260/455 R, 502.6 both of Palo Alto, Cahf. Reierences Cited [73] ASSigIICEZ OiCfOfl Corporation, P810 A110, UNITED STATES PATENTS 2,951,853 9 1960 M31501 260/3475 [22] Filed: Nov. 1, 1972 3,028,417 4/1962 Eisenmann 260/455 R 3,299,122 1 1967 Wolff 260 455 R 1 PP 302,932 3,331,865 7/1967 W611 260/455 R 3,673,237 6/1972 16111611 260/455 R Appl'camn Dam 3,781,322 12 1973 Henrick 260/455 R [63] Continuation-impart of Ser. No. 266,030, June 26,

US. C1 260/455 R Primary Examiner-Lewis Gotts Assistant Examiner-D. R. Phillips Attorney, Agent, or Firm-Donald W. Erickson; Lee-Louise H. Priest {57] ABSTRACT Aliphatic hydrocarbon tri-olefinic and aliphatic substituted di-o1efinic acids, esters, thiolesters and derivatives thereof, intermediates therefor, syntheses thereof, and the control of insects.

29 Claims, No Drawings DI- AND TRl-OLEFINIC THIOLESTERS This is a continuation-in-part of application Ser. No. 266,030, filed June 26, 1972 now abandoned, which is, in turn, a continuation-in-part of application Ser. No. 206,174, filed Dec. 8, 1971 now abandoned, which is, in turn, a continuation-in-part of application Ser. No. 187,897, filed Oct. 8, 1971, now US. Pat. No. 3,755.41 1, which is a continuation-in-part of applications Ser. No. 111,650, filed Feb. 1, 1971 now U.S. Pat. No. 3,729,486; Ser. No. 111,702, filed Feb. 1, 1971. now abandoned; Ser. No. 111,765, filed Feb. 1, 1971, now abandoned; Ser. No. 111,766, filed Feb. 1, 1971, now abandoned; Ser. No. 111,770, filed Feb. 1, 1971, now abandoned; and Ser. No. 1 15,725, filed Feb. 16, 1971 now U.S. Pat. No. 3,706,733, the entire disclosures of which are incorporated by reference.

This invention relates to novel aliphatic di-olefinic compounds, aliphatic triolefinic compounds, intermediates therefor, syntheses thereof, and the control of insects. More particularly, the novel di-olefinic compounds of the present invention are represented by the following formula:

. l 3 1 R 11 ll v -1. lfll wherein,

Z is bromo, chloro, fluoro or the group OR in which R is hydrogen, carboxylic acyl, lower alkyl, cycloalkyl, aralkyl or aryl;

Z is hydrogen, bromo, chloro or fluoro;

each of m and n is zero or the positive integer one. two or three;

each of R and R is lower alkyl;

R is alkyl;

each of R R", R and R is hydrogen or lower alkyl; and

R i 1 l 16-h 1: it;

Q is one of the groups;

n Q Q 11 7 ll 15 -CR -C-X or -C-SR in which, i

X is bromo, chloro or fluoro;

R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl, aralkyl, lower alkylthiaalkyl, lower alkoxyalkyl, halogen substituted lower alkyl, heterocyclo or a metal cation; and

R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl or aralkyl, provided that when Z is bromo, chloro or fluoro. then Z is bromo, chloro or fluoro, respectively.

The compounds of formula A are useful for the control of insects. The utility of these compounds as insect control agents is believed to be attributable to their juvenile hormone activity. They are preferably applied to the immature insect, namely, during the embryo, larvae or pupae stage in view of their effect on metamorphosis and otherwise cause abnormal development leading to death or inability to reproduce. These compounds are effective control agents for Hemipteran, such as Lygaeidae, Miridae and Pyrrhocoridae; Lepidopteran, such as Pyralidae, Noctuidae and Gelechiidae; Coleopteran, such as Tenebrionidae and Dermestidae; Dipteran, such as mosquitos, flies; Homopteran, such as aphids; and other insects. The compounds can be applied at 15 low dosage levels of the order of 0.001 ,Lg. to 25.0 pg.

per insect. Suitable carrier substances include liquid or solid carriers, such as water, acetone, xylene, mineral or vegetable oils, talc, vermiculite, natural and synthetic resins and silica. Treatment of the insects in accordance with the present invention is accomplished by spraying, dusting or exposing the insects to the vapor of the compounds of formula A. Generally, a concentration of less than 25% of the active compound is emerally employed a mixture of the C-2,3 trans and cis isomers.

ln another embodiment of the present invention, there is provided compounds of the following formula B which are useful for the control of insects in the same manner as the diolefinic compounds of formula A and which also serve as precursors for the preparation of the compounds of formula A.

In formula B, each of O, R, R R R, R, R, v m and n is the same as defined herein-above.

In the description hereinafter, each of RR, R", R R, X, Q, Z, Z, m and n is as defined hereinabove, unless otherwise specified.

As mentioned above, the compounds of formula B serve as starting materials for the preparation of compounds of formula A. The compounds of formula B can be prepared according to the syntheses described below and the examples provided hereinafter.

In one embodiment of the compounds of formula B, there is provided acids and esters represented by the formula (13'):

c=cn-c HR" in.

lll

One synthesis of esters of formula B can be outlined as follows:

l l i l 4 R c (CH2) H CH2 cu (c11 m c 0 R R14 R In the above formulas, R is lower alkyl, cycloalkyl, 0 0 12 R benzyl or phenyl and R is lower alkoxy, cycloalkoxy or H i H a I aralkoxy. P c c-R (R P-cc -R in the above synthesis, a carbonyl of formula I is re- I G (D G acted with a earbanion of formula ll to yield an ester R0 of formula B".

The earbanion (ll) is generated by treatment of the corresponding phosphonate with a base such as an alkali hydroxide, alkali hydride or alkali alkoxide, e.g. NaOl-l, Nal-l. sodium ethoxide or sodium methoxide, in an organic solvent inert to the reaction such as hydrocarbon ether or dialkylsulfoxide, solvent e.g., benzene, R O O 6 0 6 O toluene, dlmethylformamide or tetrahydrofuran. The i n reaction is generally conducted at a temperature of l:- -(;-R p-C -C-R from about 20 C to room temperature or above. The 3 reaction of the earbanion with the carbonyl (l) is gen- R O erally conducted at temperature of about 0C to room temperature or above. The phosphonates can be pre- 40 pared as described by Pattenden and Weedon, J. Chem.

Soc. (C), I984 and 1997 (1968), Still a Conversion of ll] into B" using earbanion (lIC) can be 31163569 and 3,177,226 and Corey et done using the same conditions as for conversion of] The unsaturated ketone (11]) is then reacted with a carbanion of formula "C to yield a compound of formula B" or by Wittig reaction using the ylid (11D).

Tetrahedron Letters 2,182] (1971 into [11. Wittig reactions are generally done at higher A second synthesis of esters of formula B is outlined temperatures such as from room temperature to reflux. as follows: The ylids are prepared from the corresponding phos- 3 14 fZ ?].3 12 1 1 I l (I) R -c c (CH 1 cn ca (CH c c c o /(Ill) In the second synthesis outlined above of l to lll to phonium bromide or chloride by treatment with a base B a carbonyl of formula I is reacted with a earbanion substance such as an alkali metal hydride, alkali metal of formula A using the conditions described above or hydroxide or alkali metal carbonate in an organic solwith an ylid of formula [[8 to yield an unsaturated kevent. such as toluene. benzene, or tetrahydrofuran, or

tone of formula III water or aqueous organic solvent depending upon the 5 particular base. The Wittig reagents can be prepared as described in US. Pat. No. 3,193,565.

A synthesis for esters of formula B which is applicable when each of R and R is hydrogen is outlined as l l R c c (CH CH2 cu R R OH (IV) l R is a metal such as lithium, sodium, potassium or magnesium.

In the third synthesis outlined above, an aldehyde of formula I is reacted with an alkyne of formula IV to produce the alkynyl alcohol of formula IV. A compound of formula IV is then reacted with an orthoester in the presence of weak acid catalyst to yield an allenic ester of formula V which is rearranged to 2,4- diunsaturation by treatment with base such as de scribed in copending application Ser. No. l 1 1,768, filed Feb. 1, 1971, now US. Pat. No. 3,7l6,565. Preparation of alkynyl alcohols is described by Kimel et al, J. Org. Chem. 22 1611 (1957). The conversion of alkynyl alchohols to allenic esters is described by Crandall et al, Chem. Cmm., 1411 (1970).

Another synthesis of acids and esters of formula B involves base catalyzed condensation wherein an aldehyde such as an aldehyde of formula I is reacted with an ester of the formula produced by this method are then converted into the desired ester using conventional methods such as preparation of the acid halide followed by reaction with an alcohol.

Another synthesis for acids and esters of formula B R -ll. tf a is the reaction of a ketone of formula III hereinabove with ketene to form the acid (B; R is hydrogen) which can be subjected to esterification prior to isolation of the acid, if desired, with and alcohol such as methanol, ethanol or isopropanol according to the ester moiety desired. In the practice of this synthesis, gaseous ketene is passed through an excess of the ketone (lll) containing a catalyic amount of an acid catalyst. The ketene can be diluted with an organic solvent inert to the reaction if desired. Suitable conditions and catalysts for the practice of this synthesis is described by Boese, .lr., US. Pat. No. 2,382,464.

The esters of formula B and B" are converted into the corresponding acid by hydrolysis with base such as potassium carbonate, sodium carbonate, sodium hydroxide, and the like in organic solvent such as methanol or ethanol. Other esters of the present invention can be prepared by transesterification or conversion of the acid into the acid halide by treatment with thionyl chloride, oxalyl chloride, phosphorous pentabromide or the like, and then reacting the acid halide with the alcohol corresponding to the ester moiety desired. Acyl fluorides (X is fluoro) are prepared by reacting the acyl bromide or acyl chloride with one mole anhydrous hydrogen fluoride under dry conditions and at low temperature such as about 5 for a few minutesv In a second embodiment of the novel compounds of the present invention, there is provided thio-acids and thiol esters of formula B. Thio-acids and thiol esters (Q is can be prepared from the respective acid halide using hydrogen sulfide to prepare the thio-acid and a thiol R SH in pyridine or a mercaptide to prepare the thiol ester. Thiol esters can be prepared by alkylation of the sodium salt of a thio-acid of the present invention also. See U.S. Pat. Nos. 3,567,747 and 3,505,366.

Synthesis of aldehydes and ketones of formula 1 can be accomplished using methods known in the art. Many of the carbonyl precursors of formula 1 are commercially available. The aldehydes of formula I can be prepared, for example, by oxidation, of the corresponding primary alcohol using chromic acid, manganese dioxide, or the like.

Compounds of formula I wherein m is one, two or three can be prepared utilizing carbonyl precursors as outlined below:

ra -c c (cu, 1 -Cll In the practice of the above synthesis, a carbonyl of formula X is reacted with a lower alkoxymethyltriphenylphosphonium halide such as methoxymethyltriphenylphosphonium chloride in the presence of alkyllithium, aryl lithium or the like followed by treatment with acid to afford an aldehyde of formula 1' wherein m is zero. Suitable conditions for this reaction are described by Nelson, U.S. Pat. No. 3,562,336. By repeating this reaction using the thus-prepared aldehyde as the starting material, an aldehyde of formula 1' wherein m is one is prepared. Aldehydes of formula 1' wherein m is two and three are prepared by simply repeating the foregoing reaction using the appropriate precursor of formula 1 wherein m is one and two, respectively.

Compounds of formula I wherein R is lower alkyl can be prepared by reaction of an aldehyde of formula 1; with a Grignard R MgX (R l-l) following by oxidation.

In the above process, a ketone of formula X1 is reacted with the phosphonium ylid in the presence of alkyl lithium or phenyl lithium to yield the ketal of Xll, which is treated with aqueous acid to yield the carbonyl X11.

5 The ylid (l is prepared from the chloride:

o o R Suitable procedures for the preparation of the ylid and Wittig reactions are described by A W Johnson, Ylid Chemistry," Academic Press Inc. New York (1966), U.S. Pat. Nos. 3,078,256 and 3,l30,219, Canadian Pat. No. 834,191, and Chem. Comm. 733. July 1969.

A general method for the preparation of precursors of formula I and Xlll, particularly wherein n is zero or one, is the reaction of an allyl alcohol with an enol ether. See also U.S. Pat. Nos. 2,841,620, 2,849,491 2,902,510, 2,902,515, 3,428,694, 3,493,619 and 3,574,715. A good review of the preparation of alde- 3,7-diethylnon-6-en- I l l l 1 I R C C [Cll Cll Cll (CH C O l 5 Ketones of formula X can be prepared according to methods described in the literature. A general procedure for compounds of formula X, in which n is one, two or three, can be outlined as follows (d) is phenyl 3 ,7-dimethylundec-6-en- 1 -al 2,4,5-trimethylhex-4-en 1 -al 2,4,5-trimethylhept4-en- 1 -al 3 ,5 ,6-trimethylhept-5-en- 1 -al and n is two, three or four): 3,5,6-trimetyloct-5-en-1-al l R o\ /o l 3 14 2 R 1 p-c-tcn ,-c-R R R n l l i 4 l 4 n R C=O R -C C-[Cli |'C=w 3,6-dimethylhept--en- 1 all 3,6-dimethyloct-5-en- 1 -al 2,6-dimethylhept-5-en- 1 -al 2,5 ,6-trimethylhept-5-enl-al 2,6-dimethyloct-5-en- 1 -al 4,7.8-trimethylnon-7-en-1-al 4,8-dimethylnon-7-en- 1 -al 4,8-dimethyldec-7-en- 1 -al 3.8-dimethylnon-7-enl-al 3 .8-dimethyldec-7-en- 1 -al 3,7,8-trimethyldec-7-en- 1 -al 4,9-diemthyldec-8-en- -al 3 ,9-dimethyldec-8-en- 1 -al 2,9-dimethyldec-8-enl -al t 13 I l 1 -cu l ll =0 1 v n 2 c l (c c (\II I) which is reacted with the carbanion 11A or ylid "B to prepare the unsaturated ketone (XIV) The compounds of formula A wherein Z is hydrogen and Z is halo can be prepared by treating a compound of formula B with hydrogen halide in carbon tetrachloride or other halogenated hydrocarbon solvents of low dielectric constant. The compounds of formula A wherein Z is halo can be prepared by treating a compound of formula B with bromine, chlorine or fluorine in a halogenated hydrocarbon solvent.

The compounds of formula a wherein Z is hydrogen and Z is the group -OR in which R is hydrogen can be preparedby the addition of water to the terminal olefinic bond of a compound of formula B using a mercuric salt followed by reduction of the oxymercurial intermidiate in situ. Suitable mercuric salts include mercuric acetate, mercuric nitrate, mercuric trifluoroacetate, mercuric acylates and mercuric halides. Suitable reducing agents include the borohydrides, hydrazine and sodium amalgam. See Brown and Rei, J. Am. Chem Soc. 91, 5646 (1969); Brown et al., J. Am. Chem. Soc. 89, 1522 and 1524 (1967); and Wakabayashi, J. Med. Chem. 12, l9l (January, 1969). By conducting the reaction in the presence of an alcohol (R()H) such as methanol, ethanol, isopropyl alcohol, benzyl alcohol, cyclopentano], and the like, the corresponding ether is prepared. The compounds of formula A wherein Z is OR in which R is carboxylic acyl and Z is hydrogen can be prepared from a compound of formula A wherein Z is OH and Z is hydrogen by reaction with a carboxylic acid chloride or bromide or carboxylic acid anhydride in pyridine or by treatment with a car- Reaction of a compound of formula XIV with a carbanion of formula "C or an ylid of formula llD provides esters of formula XV which serve as precursors for preparation of other compounds of formula A such as the acids, acid halides, other esters and thiolesters, using procedures described herein for the preparation of compounds of formula B.

Esters of formula XV can be prepared also by reaction of a carbanion of formula 11 with a carbonyl of formula Xlll.

In addition to the methods described herein above for preparation of the precursors of formula Xlll, the procedure of US, Pat. Nosv 2,902,495 and 3,060,237 and French Pat. No. 1,403,943. (CA 63: 16394) can be used.

The term cycloalkyl," as used herein, refers to a cyclic alkyl group of three to eight carbon atoms. The term aralkyl" refers to a monovalent hydrocarbon group in which an aryl group is substituted for a hydrogen atom of an alkyl group, such as benzyl, xylyl, mesityl, phenylethyl, methylbenzyl, naphthylmethyl and naphthylethyl containing up to 12 carbon atoms. The term aryl," as used herein, refers to an aromatic group of up to 12 carbon atoms. Typical aromatic groups include phenyl, naphthyl, lower alkylphenyl such as methylphenyl. ethylphenyl, t-butylphenyl and isopropylphenyl, lower alkylthiophenyl such as mcthylthiophenyl, ethylthiophenyl and isopropylthiophenyl, lower alkoxyphenyl such as methoxyphenyl and ethoxyphenyl, halophenyl such as chlorophenyl, bromo phenyl, iodophenyl and fluorophenyl, nitrophcnyl, and lower alkenylphenyl such as vinylphenyl and allylphenyl. In the case of substituent such as lower alkyl, lower alkythio, lower alkoxy, halo, nitro, lower alkenyl, carbonyl, lower alkoxycarbonyl, cyano, and amido can be in one or more positions of the phenyl ring, usually in the para position. The term heterocyclic," as used herein, refers to a heterocyclic group consisting of four or five carbon atoms and one heteroatom which is oxygen, nitrogen, pyrole, furan and thiophen.

The term hydroxyalkyl," as used herein, refers to an alkyl group substituted with one hydroxy group, eg hydroxymethyl, p-hydroxyethyl and 4-hydroxypentyl. The term alkoxyalkylf as used herein, refers to an alkyl group substituted with one alkoxy group, e.g. methoxymethyl, Z-methoxyethyl, 4-ethoxybutyl, npropoxyethyl and t-butoxyethyl. The term alkenyl, as used herein, refers to an ethylenically unsaturated hydrocarbon group, branched or straight chain, having a chain length of two to 12 carbon atoms, e.g. allyl, 3- butenyl, 3-hexenyl and i-propenyl. Whenever any of the foregoing terms are modified by the word lower," the chain length of the group is not more than six carbon atoms with the exception of lower alkoxyalkyl and lower alkylthiaalkyl in which event a total chain length of l2 carbon atoms is the maxium. The term halogen substituted lower alkyl, as used herein refers to a lower alkyl group substituted with one to three halogen atoms such as chloromethyl, fluoromethyl, ],l,lv trifluoroethyl 2,2,2-trichloroethyl, and the like.

The term carboxylic acyl, as used herein, refers to the acyl group of a carboxylic acid, anhydride or hal ide. The acyl group is determined by the particular carboxylic acid halide or carboxylic acid anhydride employed in the esterification. Although no upper limita tion need be placed on the number of carbon atoms contained in the acyl group within the scope of the present invention. generally it contains from one to 18 carbon atoms. Typical esters of the present invention include formate, acetate, propionate, enanthate, benzoate, trimethylacetate, trichloroacetate, trifluoroacetate, t-butylacetate, phenoxyacetate, cyclopentylpropionate, aminoacetate, B-chloropropionate, adamantoate, octadec-J-enoate, dichloroacetate, butyrate, pentanoate, hexanoate, phenylacetate, pmethylbenzoate, B-phenylpropionate, 3,4dimethylbenzoate, p-isopropylbenzoate, cyclohexylacetate, sterarate, methacrylate, p-chloromethylbenzoate, pmethoxybenzoate and p-nitrobenzoate.

The term metal, as used herein, refers to lithium, sodium, potassium, calcium, strontium, copper, manganese and zinc. The term alkyl refers to a branched or straight chain, saturated aliphatic hydrocarbon of one to 12 carbon atoms. The term lower alkyl refers to an alkyl group having a chain length of one to six car bon atoms. The term lower alkynyl" refers to a mono acetylenically unsaturated aliphatic hydrocarbon hav ing a chain length of three to six carbons.

In addition to the compounds of the present invention having activity useful for the control of insects. the compounds of formula A and B have numerous other useful applications. For example, the esters of formula B of the present invention are useful lubricants and plasticizers for polymers, such as SBR, polybutadiene, ethylene-propylene copolymers and polypropylene and aid in the processing and application of polymers. Thiolesters of formula A and B possess excellent lubricating properties per se and are also useful as lubricant additives.

The presence of an olefinic bond at position C2 and C-4 C4 the compounds of formula A give rise to four isomers each of which is embraced by the present invention. The presence of three olefinic bonds in compounds of formula B give rise to eight isomers, each of which is embraced by the present invention. As mentioned above, a mixture of isomers is suitably employed for the control of insects such as a mixture containing the trans (2), trans (4) isomer and the cis (2), trans (4) isomer. The conditions of the syntheses described herein and the reactants can be selected so as to favor formation of one isomer such as the all trans isomer over the formation of other isomers, The selection of appropriate conditions and reactants to favor formation of one isomer over another will be apparent to those of ordinary skill in the art giving due consideration to the specific examples hereinafter. See also Pattenden and Weedon, supra and Corey et al, supra. In the specific examples hereinafter, when isomerism is not specified, it is understood to include a mixture of isomers which, if desired, can be separated using known separation methods. Hereafter, when only one designation of configuration is given, the designation refers to position C-2,3 and the configuration is taken to be trans at position C-4,5 when not otherwise specified. The use of trans/cis and cis/trans" is with reference to position C-2,3 and indicates a mixture of isomers.

The following examples are provided to illustrate the practice of the present invention. Temperature is given in degrees Centigrade.

EXAMPLE I To a mixture of one g. of 3,7-dimethyloct6-en-l-al 1.5 g. of phosphonate (II; R is ethyl, R is methyl, R is ethoxy, R is hydrogen) and 50 ml. of dimethylformamide, under nitrogen, is slowly added sodium ethoxide (prepared from 200 mg. of sodium and 12 ml. of ethanol). The mixture is allowed to stand at room temperature for 1 hour and then is worked up with ether. The ethereal extracts are dried, concentrated and then chromatographed on silica plates eluting with hexane/ether to yield ethyl 3,7,1 l-trimethyldodeca-2,4,10- trienoate which is predominantly trans at position C-2,3 and C-4,5.

By using diethyl 3 methoxycarbonyl-2-methylprop-2- enyl phosphonate and sodium methoxide, there is pre pared methyl 3,7,l l-trimethyldodeca-2,4,lO-trienoate.

EXAMPLE 2 The process of Example 1 is repeated using each of the aldehydes under column I as the starting material to yield the respective ester under column ll 3 7 dimethylnon-6-en-lal 3ethyl-7-methylnon-6-en- 1 -al 3 .7-diethylnon-6-en- 1 -al 4,8-dimcthylnon-7-en-l -al 3,6-dimethylhept-5-enl-al 3,6-dimethyloct-5-enl a! 2,6-dimethylhept-5-en- 1 -al ethyl 3,7,] l -trimethyltrideea-2,4, l O-trienoate ethyl 3,] l-dimethyl-7-ethyltrideca-2,4, l O-trienoate 13 ethyl 7,1 l-diethyl-3-methyltrideca 2,4,l-trienoate ethyl 3.8. l 2-triemthyltrideca-2,4,l l-trienoate ethyl 3.7, l O-trimethylundeca-2,4,9-trienoate ethyl 3 ,7, l O-trimethyldodeca-2,4,9-tricnoate ethyl 3,6,10-trimethylundeca-2,4,9-trienoate EXAMPLE 3 A mixture of l g. of trans/cis methyl 3,7,11- trimethyldodeca-2,4,lO-trienoate, 60 ml. of methanol, 0.5 g. of potassium hydroxide and 6 m1. of water is heated at reflux for about 8 hours. The mixture is then diluted with water, neutralized and extracted with ether. The organic phase is washed with water, dried over sodium sulfate and evaporated to yield trans/cis 3,7,1 l-trimethyldodeca-2,4, lO-trienoic acid.

Using the foregoing procedure, the other esters of Example 2 are hydrolyzed to produce the respective free acids under column 111.

Ill

3,7,1 l-trimethyltrideca-2,4- l O-trienoic acid 3,1 1 -dimethyl- 7-ethyltrideca-2,4, 1 O-trienoic acid 7,1 1-cliethy1-3-methyltrideca-2,4, lO-trienoic acid 3,8, 1 2-trimethy1trideca-2,4,1 l-trienoic acid 3,7, 10-trimethylundeca-2,4,9-trienoic acid 3,7,10-trimethyldodeca-2,4,9-trienoic acid 3,6,l0-trimethylundeca-2,4,9-trienoic acid EXAMPLE 4 1 gram of thionyl chloride is added with stirring at room temperature to 0.5 g. of trans/cis 3,7,1l-trirnethyld0deca-2,4, IO-trienoic acid and the mixture heated at about 50 for 10 minutes. Excess thionyl chloride is removed by evaporation and then t-butyl alcohol (about 2 equivalents) is added and the mixture heated at about 50 for about 5 minutes to yield t-butyl 3,7,1 1- trimethyldodeca-2,4, l O-trienoate (trans/cis).

By using other alcohols in place of tbutyl alcohol in the process of this Example, such as cyclohexyl alcohol, isopropyl alcohol, benzyl alcohol, n-pentanol, nhexanol, or n-propanol, the respective esters are prepared, i.e.,

cyclohexyl 3,7,1 1-trimethyldodeca-2,4, l O-trienoate isopropyl 3,7,1 l-trimethyldodeca-2,4, l O-trienoate benzyl 3,7,1 l-trimethyldodeca-2,4, 1 O-trienoate n-pentyl 3,7,1 1-trimethy1dodeca-2,4, l0trienoate n-hexyl 3,7,1 1-trimethyldodeca-2,4, 1 O-trienoate n-propyl 3,7,1 1-trimethyldodeca-2,4, l O-trienoate EXAMPLE 5 To a solution of 0.5 g. of trans/cis 3,7,1l-trimethyldodeca-2,4,10-trienoic acid in ml. of benzene is added with stirring an equivalent amount of potassium bicarbonate. The mixture is stirred until the evolution of carbon dioxide ceases and then evaporated to yield potassium 3,7,1 1 -trimethyldodeca-2,4, lO-trienoate.

Alternatively, acid salts can be prepared by titratin g the acid with an organic solution or aqueous organic solution of the desired metal.

EXAMPLE 6 One gram of 3,7,1l-trimethyltrideca-2,4,lO-trienoic acid in 30 ml. of benzene and one mol of sodium hydride is stirred about 2 hours and then a slight excess of oxalyl chloride is added at about 0 and stirred for 1 hour. The product is worked up by removal of solvent in vacuo and extraction with pentane to yield 3,7,11 trimethyltrideca-2,4, l O-trienoyl chloride.

EXAMPLE 7 A. To magnesium propynylide (15 g.) in 150 ml. of ether is slowly added 0.3 moles of 3,7-dimethyloct-6- en-l-al and the mixture then stirred overnight. Satu rated aqueous ammonium chloride is added and the layers separated. The organic phase, combined with ether backwashings of aqueous phase, is washed with water, dried and solvent evaporated to yield 6,10- dimethyl-9-undecen-2-yn-4-ol which can be purified by chromatography.

B. A mixture of 18.5 g. of the alkynyl alcohol of part A, g. of triethylorthoacetate and 0.7 g. of propionic acid is refluxed under a spinning band column to remove ethanol as it is formed. After the elimination of ethanol is about complete, the crude reaction product is distilled under vacuum to yield ethyl 3,7,1 1- trimethyldodeca-3,4,IO-trienoate. Alternatively, the crude reaction product is purified by chromotography on silica.

C. A solution of 1.0 g. of the allenic ester of part B in 20 ml. of ethanol is treated with 4 ml. of aqueous 2N sodium hydroxide and left at room temperature for several minutes. The mixture is then poured into pentane and washed with saturated brine and separated. Evaporation of the organic phase yields ethyl 3,7,1 1- trimethyldodeca-2,4, 1 O-trienoate.

EXAMPLE 8 The process of Example 7, part A, is repeated using each of the aldehydes under column 1 as the starting material to yield the respective alkynyl alcohol under column 1V, each of which is reacted with triethylorthoacetate using the process of Example 7, part B, to prepare the respective allenic ester under column V.

6, l 0-dimethyl-9-dodecen-2-yn-4-ol 6-methyll O-ethyl-9-dodecen-2-yn-4-ol 6,1 O-diethyl-9-dodeccn-2-yn-4-ol 7,1 l-dimethyl-10-dodecen-2-yn-4-ol 6,9-dimethyl-8-decen-2-yn-4-ol 6,9-dimethyl-8-undecen-2-yn4-ol 5,9-dimethyl-8-decen-2yn-4-ol ethyl 3,7,1 l-trimethy1trideca-3,4, IO-trienoate ethyl 3,1 l-dimethy1-7-ethyltrideca-3 ,4, l O-trienoate ethyl 3-methyl-7,l l-diethyltrideca-3 ,4, l O-trienoate ethyl 3,8,12-trimethy1trideca-3,4,1 1 -trienoate ethyl 3,7, 10-trimethylundeca-3,4,9-trienoate ethyl 3,7,10-trimethyldodeca-3,4,9-trienoate ethyl 3,6, 10-trimethylundeca-3,4,9-trienoate Using the process of Example 7, part C, each of the allenic esters under column V is rearranged by treatment with aqueous sodium hydroxide to produce the respective a, B-unsaturated ester.

EXAMPLE 9 To 126 mg. of a 57% dispersion of sodium hydride in oil is added pentane. The pentane is removed and the sodium hydride washed several times with pentane. To the washed sodium hydride is added 582 mg. of diethyl acetyl-methylphosphonatc (11A; R is ethyl, R is methyl, R is hydrogen) in 5 ml. of tetrahydrofuran at -10 under argon. After several minutes, the solution is transferred to a solution of 425 mg. of 3,7-dimethyloct-6-en-l-al in about 4 ml. of dry tetrahydrofuran under argon over a period of about 20 minutes at room temperature. After about 2 hours, water is added followed by addition of ether and the layers separated. The organic layer is washed with saturated sodium chloride, dried over sodium sulfate and evaporated under reduced pressure to yield 6,10-dimethylundeca- 3,9-dien-2-one.

EXAMPLE 10 One gram of triphenylphosphineacetylmethylene and 425 mg. of 3,7-dimethylnon-6-enl-al are dissolved in 10 ml. toluene and refluxed under nitrogen overnight. The toluene is distilled off and the formed triphenylphosphine oxide crystallized by addition of pentane. Filtration and evaporation of the pentane gives a residue, which is further purified by preparative thin layer chromatography to yield 6,10-dimethyldodeca-3,9- dien-IZ-one.

EXAMPLE 1 1 41 Grams of 3,7-dimethyloct-6en-l-al and 80 g. of recrystallized (ethyl acetate) triphenylphosphineacetyl-methylene [Ramirez et al., J. Org. Chem. 22, 41 1957) are refluxed in one liter of dry toluene for 18 hours, under nitrogen. Most of the solvent is removed in vacuo, 500 ml. pentane is added and the mixture filtered. The flask and the triphenylphosphine oxide filter cake are washed several times with pentane. The filtrate is concentrated under vacuum to yield 6,10- dimethylundeca-3,9-dien-2-one.

EXAMPLE 12 Using the process of either of Example 9, 10 or l 1, each of the aldehydes under column I is converted into the respective di-unsaturated ketone under column V1v 6, l -dimethyldodeca3 ,9-dien-2-one 6methyllO ethy1dodeca-3,9-dien-2-one 6,10-diethyldodeca-3 ,9-dien-2 one 7.1 l-dimethyldodeca-B, l O-diemZ-one 6.9-dimethyldeca-3 ,8-dien-2-one 6,9-dimethylundeca-3 ,8-dien-2one 5 ,9-dimethyldeca-3,S-dien-Z-one EXAMPLE 13 The carbanion of diethyl carbomethoxymethyl phosphonate is reacted with 6,lO-dimethylundeca-3,9-dien- 2-one and each of the ketones under column V1 using the procedure of either Example 1 or 9 to prepare the respective methyl esters under column Vll.

Vll

methyl 3,7,1 l-trimethyldodeca-2,4, l O-trienoate methyl 3,7 ,1 Ltrimethyltrideca-ZA, IO-trienoate methyl 3,1 1-dimethyl-7-ethyltrideca-2,4,l0-

trienoate methyl 3-methyl-7,l l-diethyltrideca-2,4, l 0- trienoate methyl 3,8, l 2-trimethyltrideca-2,4,l l-trienoate methyl 3,7,lO-trimethylundeca-2,4,9-trienoate methyl 3,7, l O'trimethy1dodeca-2,4,9-trienoate methyl 3,6,10-trimethy1undeca-2,4,9-trienoate EXAMPLE 14 Anhydrous hydrogen chloride is bubbled into 100 ml. of dry carbon tetrachloride at 0 until six equivalent is taken up. Five grams of trans ethyl 3.7,l1-trimethyldodeca-2,4, l O-trienoate is added and the resulting mixture allowed to stand for about 48 hours at 0. The mixture is evaporated under reduced pressure to yield trans ethyl l l-chloro-3,7,l l-trimethyldodeca-2,4- dienoate which is purified by chromatography.

The above process is repeated using each of the unsaturated esters under Column 11 to prepare the respective compound under Column V111.

ethyl l l-chloro-3,7,1 1trimethyltrideca-2,4-

dienoate,

ethyl l l-chloro-3,l l-dimethyl-7-ethyltrideca-2,4-

dienoate,

ethyl 1 l-chloro-7,l 1-diethyl-3-methyltrideca-2,4-

dienoate,

ethyl l2-chloro-3,8,1 2-trimethyltrideca-2,4

dienoate,

ethyl lO-chloro- 3 ,7, lO-trimethylundeca-2,4-

dienoate,

ethyl lO-chloro-3,7,10-trimethyldodeca-2,4-

dienoate, and

ethyl lO-chloro-3 ,6,10-trimethylundeca-2,4-

dienoate.

Each of the esters under col. V11 is used as the starting material in the process of this example to prepare the hydrochlorides under col. 1X.

trienoate, cyclohexyl 3,7,1l-trimethyldodeca-2,4,10- trienoate and n-hexyl 3,7,lO-trimethylundeca-2,4,9- trienoate is used as the starting material in the procedure of Example 14 to prepare the respective compound, that is:

benzyl l l-chloro-3,7,1 l-trimethyltrideca-2,4-

dienoate,

isopropyl l l-chloro-3,7,1 l-trimethyldodeca-2,4-

dienoate,

cyclohexyl 1 l-chloro-3,7,l 1-trimethy1dodeca2,4-

dienoate, and

nhexyl lO-chloro-3 ,7, l 0-trimethylundeca-2 ,4-

dienoate.

EXAMPLE 16 One gram of trans ethyl 3,7,1 l-trimethyldodeca- 2,4.10-trienoate is added to a solution of 1 equiv. of dry hydrogenfluoride in dry tetrahydrofuran. The mixture is allowed to stand at 0 for 15 hours and is then washed with water, dried and evaporated under reduced pressure to yield trans ethyl 1 1-fluoro-3,7,l l-trimethyL dodeca-EA-dienoate which can be purified by chromatography.

EXAMPLE 17 The process of Example I4 is repeated with the exception of using dry hydrogen bromide in place of hydrogen chloride to yield trans ethyl l l-bromo-3,7,l 1- trimethyldodcca-2,4-dienoate.

By treating the l l-bromide with anhydrous silver fluoride in acetonitrile under reflux conditions for about 6 hours, there is prepared trans ethyl l l-fluoro-3,7,l ltrimethyldodeca-2,4-dienoate.

EXAMPLE l8 Chlorine gas is bubbled into 200 ml. of carbon tetrachloride at until one equivalent is taken up. Twentyfive grams of trans ethyl 3,7,] l-trimethyldodeca- 2.4. (Hrienoate is added and the mixture is then stirred and then allowed to stand at about 0 for 24 hours. The mixture is then evaporated to yield trans ethyl l0,l ldichloro-3,7,l l-trimethyldodeca-2,4dienoate which can be purified by chromatography.

EXAMPLE 1) To a mixture of g. of trans ethyl 3,7,1 l-trimethyldodeca-2,4.l0-trienoate in 100 ml. of fluorotrichloromethane is slowly added 1 equiv. of dry fluorine in about one hour at about 78. After stirring the mixture at this temperature for about 16 hours, the resultant mixture is evaporated and chromatographed on silica to yield trans ethyl 10,l l-difluoro-3,7,l ltrimethyldodeca-ZA-dienoate.

By using bromine in the process of Example 18 there is prepared trans ethyl l0,ll-dibromo-3,7,1ltrimethyldodeca-2,4-dienoate.

EXAMPLE 20 To a mixture of 1.9 g. of mercuric acetate, 6 ml. of water and 20 ml. of tetrahydrofuran is added 1.49 g. of trans ethyl 3,7,1 l-trimethyldodeca-2,4,lO-trienoate slowly. After addition is complete, the reaction mixture is stirred for about 20 minutes. The mixture is cooled to about 0 and 6 ml. of aqueous sodium hydroxide (3 molar) is added followed by 0.49 g. of sodium borohydride in aqueous sodium hydroxide (about 3 molar). The mixture is stirred for about 30 minutes. The mixture is then decanted, concentrated, diluted with water and then extracted with ether. The ethereal extract is washed with water, dried over magnesium sulfate and the product chromatographed on silica gives ethyl l lhydroxy-3,7,l 1-trimethyldodeca-2,4-dienoate (trans).

The above process is repeated using each of the unsaturated esters under Column II to prepare the respective compound under Column X.

ethyl l l-hydroxy-3,7,l l-trimethyltrideca-2A- dienoate,

ethyl l l-hydroxy-3,l l-dimethyl-7-ethyltrideca-2,4-

dienoate,

ethyl l l-hydroxy-7,l l-diethyl-3-methyltrideca-2,4-

dienoate,

ethyl l2-hydroxy-3,8, l 2-trimethyltrideca-2A- dienoate,

ethyl lO-hydroxy-3,7, l 0-trimethylundeca-2,4-

dienoate.

ethyl l0-hydroxy3,7, l 0-trimethyldodeca-2A- dienoate. and

ethyl l 0-hydroxy-3,6. l O-trimethylundeca-ZA- dienoate.

EXAMPLE 2] Each of the esters under Column Vll is used as the starting material in the process of Example 20 to prepare the respective hydroxyl under Column XI:

trienoate, cyclohexyl 3,7,1 l-trimethyldodeca-2,4,l0- trienoate and n-hexyl 3,7.l0-trimethylundeca-2,4,9- trienoate is used as the starting material in the process of Example 20 to prepare the respective hydroxy, that benzyl l l -hydroxy-3 ,7, l l-trimethyltrideca-2,4-

dienoate.

isopropyl l 1-hydroxy-3,7,l l -trimcthyldodeca-2,4-

dienoate,

cyclohexyl l lhydroxy-3,7,l l-trimethyldodeca-2,4-

dienoate, and

n-hexyl l0-hydroxy-3 ,7. lO-trimethylundeca'2,4

dienoate.

EXAMPLE 23 To a solution of 2 g. of trans ethyl 3,7,1 l-trimethyldodeca-2,4,lO-trienoate in 20 ml. of ethanol, cooled to 0 in an ice bath, is added a suspension of 2.32 g. of mercuric acetate in 50 ml. of ethanol over 15 minutes. The reaction mixture is stirred for two hours and then, with cooling, 1.22 g. of potassium hydroxide in 20 ml. of ethanol is added. Then 0.139 g. of sodium borohydride is added in small portions and stirring continued for 30 minutes. The solution is decanted. then concentrated to half volume, diluted with [00 ml. of water and extracted with ether (3 X 50). The ethereal phase is washed with water, dried over magnesium sulfate and the crude product chromatographed on silica using hexane:ether to yield trans ethyl l l-ethoxy-3,7,l ltrimethyldodeca-2,4-dienoate.

EXAMPLE 24 A mixture of l g. of trans ethyl ll-hydroxy-3,7,l ltrimethyldodeca-2,4-dienoate, l0 ml. of acetic anhydride and 0.5 g. of dry sodium acetate is refluxed for about 5 hours. After cooling, excess anhydride is re moved by vacuum and the residue extracted with ether. The ethereal extract is washed, dried over magnesium sulfate and evaporated to yield the corresponding acelate, trans ethyl l 1-acetoxy-3,7,l l-trimethyldodeca- 2,4-dienoate.

EXAMPLE 25 A mixture of 2 g. of dry trans ethyl ll-hydroxy- 3,7,11-trimethyldodeca-2.4-dienoate, ml. of acetyl ch oride and ml. of dry pyridine under nitrogen is heated on a steam bath for about 6 hours. After cooling, the mixture is concentrated under vacuum and the residue taken up in ether. The ethereal extract is washed. dried over magnesium sulfate and evaporated to yield the corresponding acetate, trans ethyl l1- acetoxy-3,7,1 ltrimethyldodeca 2,4-dienoate.

The process of this example is repeated with the ex ception of using triethylamine in place of pyridine to yield the 1 l-acetate.

EXAMPLE 26 One gram of trans ethyl 11-hydroxy-3,7,l1- trimethyldodeca-l-Ldienoate in 10 ml. of diglyme is added dropwise to a slurry of 1 gv of sodium hydride in 10 ml. of diglyme under nitrogen. To this mixture is added 0.9 g. of cyclohexylchloridet The reaction mixture is stirred at about for minutes and then quenched in ice water. The organic phase is separated and aqueous phase re-extracted with ether. The organic materials are washed with water, dried over sodium sulfate and evaporated to yield the cyclohexyl ether of trans ethyl l 1-hydroxy-3,7,1 l-trimethyldodeca 2,4-dienoate.

By using each of benzyl chloride and cyclopentyl chloride in the foregoing procedure, the corresponding benzyl ether and cyclopentyl ether is prepared.

EXAMPLE 27 By use of the procedure of Example 25, ethyl 1 lhydroxy-3,7,11-trimethyldodeca-2,4-dienoate is converted into the corresponding ll-chloroacetate, 1 1 dichloroacetate and ll-trichloroacetate using chloroacetyl chloride, dichloroacetyl chloride and trichloroa cetyl chloride, respectively.

The respective 1 l-trifluroracetate, propionate, nbutanoate, n-pentanoate and n-hexanoate esters of ethyl 1 1-hydroxy-3,7,1 1-trimethyldodeca-2,4-dienoate are prepared according to the process of Example 24 using trifluoroacetic anhydride, propionic anhydride, n-butyric anhydride, n-pentanioc anhydride and n hexanoic anhydride or according to the process of Example 25 using the corresponding acid chloride.

EXAMPLE 28 A mixture of 20 ml. of dry formic acid and 2 g. of trans ethyl 3,7,1l-trimethyldodeca-2,4,IO-trienoate is heated at for 2 hours and then poured onto ice cold potassium bicarbonate solution. The reaction is worked up by extraction with ether, washing the ethereal ex tract, drying over magnesium sulfate and evaporation to yield the formate of trans ethyl l 1-hydroxy-3,7,l 1 trimethyldodeca-2.4-dienoate.

Using the above process. the formates of formula A are prepared from the corresponding precursor of formula B having a terminal olefmic bond.

EXAMPLE 29 Fifteen grams of mercuric acetate in 50 ml. of dry ethanol is added to 12 g. of trans ethyl 3,7,11-

trimethyldodeca-2,4,IO-trienoate in 30 ml. of dry ethanol cooled in an ice bath. The temperature is allowed to come to room temperature by standing overnight.

Then the mixture is cooled to 0, 10 g. of potassium by 5 droxide in 150 ml. of ethanol is added followed by addition of 1.0 g. of sodium borohydride in small portions. After about 30 minutes at 0, water is added and mixture left at room temperature for 2 hours. The mixture is filtered, filtrate concentrated and extracted with ether. The ethereal extract is washed, dried, and evapo rated to yield trans ethyl ll-ethoxy-3,7,l l-trimethyldodeca-2,4-dienoate which is purified by distillation or chromatography.

By using methanol in the foregoing process in place of ethanol, there is prepared the respective 1 l-methyl ether. in the same way, each of isopropanol, t-butanol, and n-propanol is added to the terminal double bond to prepare: 20 ethyl l l-isopropoxy-3,7,1 1-trimethy1dodeca-2,4-

dienoate, ethyl l 1-t-butoxy-3 ,7,1 1trimethyldodeca-2,4-

dienoate, and ethyl 1 l-n-propoxy-3 ,7,1 1-trimethyldodeca-2,4-

25 dienoate EXAMPLE 30 Each of the tri-unsaturated esters under col. VII is used as the starting material in the process of Example 2] or 29 to yield the respective ethoxy substituted compound under col. XI].

Xll

g. of potassium hydroxide and 6 ml. of water is heated at reflux for about 8 hours. The mixture is then diluted with water, neutralized and extracted with ether. The organic phase is washed with water, dried over sodium sulfate and evaporated to yield trans 1 1-ethoxy-3,7,l 1- trimethyldodeca-2.4-dienoic acid.

EXAMPLE 32 Using each of the esters under Column ll as the starting material in the process of either Example 22 or 29, there is prepared the respective substituted ester under Column Xlll.

XIII

ethyl l l-ethoxy-3,7,l l-trimethyldodeca-2,4-

dienoate, ethyl I l-ethoxy-3,7,l l-trimethyltrideca-2,4-

dienoate, ethyl l lethoxy-3,l l-dimethyl-7-ethyl trideca-2,4-

dienoate, ethyl l l-ethoxy-7,l l -diethyl-3-methyltrideca-2,4-

dienoate, ethyl l2-ethoxy-3 ,8 l 2trimethyltrideca-2 ,4-

dienoate, ethyl l-ethoxy-3 ,7, l O-trimethylundeca-2,4-

dienoate, ethyl l0-ethoxy-3,7, l O-trimethyldodeca-2,4-

dienoate, and ethyl l0-ethoxy-3,6, l 0-trimethylundeca-2,4-

dienoate.

EXAMPLE 33 A. To a mixture of 50 g. of 7-methoxy-3,7- dimethyloctan-l-al, 75 g. of diethyl 3-ethoxycarbonyl- Z-methylprop-Z-enyl phosphonate (49% trans), and 500 ml. of dimethylformamide, under nitrogen, at 0, and with stirring, is slowly added 9 g. of sodium in 250 ml. of ethanol. After addition is complete, the reaction is allowed to continue 1 hour at room temperature. The reaction is worked up with hexane, filtered through Florisil and filtrate evaporated to yield trans(2), trans(4) and cis(2), trans(4) ethyl 1 l-methoxy-3,7,l ltrimethyldodeca-2,4-dienoate (about 60% trans, trans).

B. A mixture of 45 g. of the ethyl ester of part A, 350 ml. of ethanol, 100 ml. of water and 70 ml. of 50% aqueous NaOH is refluxed for 22 hours. Ethanol is then removed under reduced pressure, water added followed by extraction with ether. The aqueous phase is adjusted to about pH 8 using aqueous HCl and 31 g. of S-benzyLisothiouronium hydrochloride in water is added. The thus-formed salt is filtered, washed with water, recrystallized from aqueous methanol (twice) and then treated with aqueous HCl/ether and worked up to yield ll-methoxy-3,7,ll-trimethyldodeca-2,4-

dienoic acid which crystallizes on cooling.

C. The acid (0.5 g.) of part B is methylated using diazomethane in ether, followed by chromatography on prep. TLC and distillation (short path) to prepare methyl 1 l-methoxy-3,7,l l-trimethyldodeca-2,4- dienoate [95.2% trans(2), trans(4)]. In the same way, using diazoethane is prepared ethyl ll-methoxy- 3,7,l l-trimethyldodeca-2,4-dienoate [95.2% trans(2), trans(4)].

EXAMPLE 34 To 0.5 g. of the acid of Example 33 in 10 ml. of benzene, under nitrogen, is added 0.055 g. of sodium hy dride. After stirring at room temperature for minutes, 0. 17 ml. of oxalyl chloride is added followed by stirring for 2.5 hours. Then 2 ml. of isopropanol is added. After about 3 hours, the reaction is worked up by extraction with ether, washing with sodium bicarbonate and brine, drying over calcium sulfate and isolation to yield isopropyl 1l-methoxy-3,7.ll-trimethyldodeca-2,4-dienoate (about 91% trans, trans).

EXAMPLE 35 To 0.5 g. of the acid of Example 33 in IQ ml. of benzene, under nitrogen is added 0.17 ml. of oxalyl chloride which is stirred for about 45 minutes and then allowed to stand 2 hours. Two ml. of isopropanol is added. After 3 hours, ether is added and organic layer separated. The organic layer is washed with aqueous sodium bicarbonate and brine, dried over calcium sulfate and concentrated under reduced pressure to yield isopropyl l l-methoxy-3,7,l l-trimethyldodeca2 ,4- dienoate (about 91% trans, trans) which can be purified by chromatography and distillation.

Using the foregoing precedure, each of 3- thiacyclohexanol, 2,2,2-trifluoroethanol, t-butanol, 2- methoxyethanol, 2-methylthioethanol and s-butanol provides 3'thiacyclohexyl l l-methoxy-3,7,l ltrimethyldodeca-2,4-dienoate, 2',2',2'-trifluoroethyl l l-methoxy-3 ,7,l l-trimethyldodeca-2,4-dienoate, t' butyl l l-methoxy-3,7,l l-trimethyldodeca-2,4- dienoate, 2'-methoxyethyl l l-methoxy-3,7,l l trimethyldodeca-2,4-dienoate, 2'-methylthioethyl 1 lmethoxy 3,7,1l-trimethyldodeca-2.4-dienoate, and sbutyl 1 l-methoxy-3,7,l l-trimethyldodec a-2,4- dienoate. Each of the esters is primarily the trans(2), trans(4) isomer.

EXAMPLE 36 Sodium ethoxide (prepared from 0.2 g. of sodium and I2 ml. of ethanol) is slowly added to a mixture of L] g. of 7-ethoxy-3,7-dimethyloctan-l-al, diethyl 3- ethoxycarbonyl-2-methylprop'2-enyl phosphonate and 50 ml. of dimethylformamide, with stirring, under nitrogen, at 0. The reaction is stirred for 1.5 hours after addition is complete and then worked up by extraction with ether to yield ethyl ll-ethoxy-3,7,l l-trimethyldodeca-2,4-dienoate, mostly trans(2), trans(4), which can be further purified by chromatography and distillation.

EXAMPLE 37 To a mixture of 10 g. of 7methoxy-3.7 dimethyloctan-l-al, 17 g. of diethyl 3-ethoxycarbonyl- 2-methylprop-2-enyl phosphonate (77% trans), and 150 ml. of dimethylformamide, under nitrogen, 0, with stirring, is added sodium isopropanolate (prepared from 1.5 g. of sodium in 150 ml. of isopropanol). After addition is complete, the reaction is stirred for [8 hours at room temperature and then worked up by extraction with hexane to yield isopropyl l l-methoxy-3,7,l ltrimethyl-dodeca-Z,4-dienoate (mostly trans-2,trans- 4), which can be chromatographed and distilled for further purification.

EXAMPLE 38 A mixture of 5 g. of hydroxycitronellal (7-hydroxy- 3,7-dimethyloctan-lal), 8.5 g. of di-isopropyl 3- ethoxycarbonyl-2-methylprop-2-enyl phosphonate, and 40 ml. of dimethylformamide, under nitrogen and cooled in an ice-bath, is stirred for 0.5 hour and then ground NaOH (l.l65 g.) is added. The reaction mixture is stirred at room temperature for three hours and then hexane/water (l/l) added. The organic layer is washed with water and brine, dried over calcium sulfate and concentrated. The concentrate is filtered through Florisil using hexane and hexane-ether. The filtrate is concentrated and then distilled to yield ethyl l l-hydroxy-3,7,l l-trimethyldodeca-2,4-dicnoate (about trans-2, trans-4).

The process of this example is repeated with the ex ccption of using di-isopropyl 3-isopropoxycarbonyl-2- methylprop-Z-enyl phosphonate to prepare isopropyl l l-hydrox v3 ,7,l 1-trimethyldodeca-2.4-dienoate, about 78% trans(2), trans(4) and 21% cis(2), trans(4).

EXAMPLE 39 To 40 ml. of ice cold isopropano] is added 2.49 g. of acetyl chloride. The resulting solution is stirred at for 15 min. and 1.0 g. of trans isopropyl 3,7,1 1- trimethyldodeca 2,4,lO-trienoate added. The solution is stirred for 1 hour at 0 and for 48 hours at 25. Solvent is removed under reduced pressure and the concentrate taken up in hexane. The hexane solution is washed with water until the aqueous wash is neutral and then with brine. The solution is dried over calcium sulfate and solvent evaporated to yield trans isopropyl 1 1-chloro-3.7,l ltrimethyldodeca-2,4-dienoate.

EXAMPLE 40 A. 100 Grams of 3,7dimethyloct-6-en-1-01 is dissolved in 150 ml. of pyridine and 100 ml. of acetic anhydride and left at room temperature for about 48 hours. Then the mixture is extracted with ether and the ethereal extracts washed with water, aqueous HCl and brine to yield lacetoxy-3,7-dimethyloct-6-ene which is purified by distillation.

B. 150 Grams of mercuric acetate in 400 ml. of dry ethanol is added to 100 g. of l-acetoxy3,7- dimethyloct-o-ene (citronellol acetate) in 200 ml. of dry ethanol cooled in an ice bath. The temperature is allowed to come to room temperature by standing overnight. Then the mixture is cooled to 0, 100 g. of potassium hydroxide in 1.51. of ethanol is added followed by addition of 10 g. of sodium borohydride in small portions. After about 30 minutes at 0, water (100 m1.) is added and mixture left at room temperature for 2 hours. The mixture is filtered, filtrate concentrated and extracted with ether. The ethereal extract is washed, dried and evaporated to yield 7-ethoxy-3,7- dimethyloctan-l-ol which is purified by distillation or chromatography.

By using methanol in the foregoing process in place of ethanol, there is obtained 7-methoxy-3,7-dimethyloctan-l -ol.

C. A mixture of 1.9 of 7-ethoxy-3,7-dimethyloctan-1- 01 and 10 ml. of pyridine is added to a suspension of 8.0 g. of chromium trioxide in 100 ml. of pyridine with stirring under nitrogen. After about 4 hours at room temperature, the reaction is poured into saturated sodium bicarbonate and worked up with ether followed by washing with 2N NaOH, water, 10% HCl, water and brine and evaporated under reduced pressure to dryness and then filtered with hexane to yield 7-ethoxy- 3,7-dimethyloctanl -a1.

D. A mixture of 9.0 g. of 7-ethoxy-3,7- dimethyloctan-l-al and g. of triphenylphosphineacetylmethylene in 100 ml. of dry toluene, under nitrogen, is refluxed for hours. Thereafter, the toluene is evaporated and pentane added to remove triphenylphosphine. After concentration, the product is distilled to yield lO-ethoxy-o,10-dimethy1undec-3-en- 2-one. The thusprepared ketone is reacted with the carbanion of diethyl carbethoxymethylphosphonate using the procedure of Example l or 9 to prepare ethyll l-ethoxy-3.7,1 1-trimethyldodeca-2,4-dienoate.

EXAMPLE 41 Each of the aldehydes under col. XIV is reacted with the carhanion of di-isopropyl 3isopropoxycarbonyl-2- methylprop-2-enyl phosphonate using the procedure of Example 38 to prepare the respective isopropyl ester under col. XV.

XIV

3 ,6,7-trimethyloct-6-en- 1 a1 3,6,7-trimethyln0n-6-enl -al 2,5-dimethylhex-4-en- 1 -al 2,4,5-trimethyl-4-enl a1 3 ,5,6-trimethy1hept-5-en- 1 -al 2,5,6-trirnethylhept-5-en-1-a1 3 ,8-dimethylnon-7'en- 1 -a1 3 ,9-dimethyldec-8-en- 1 -al isopropyl 3,7,10, 1 Ltetramethyldodeca-ZA, l 0- trienoate isopropyl 3.7,10,1 l-tetramethyltrideca-2,4,10-

trienoate isopropyl 3,6,9-trimethyldeca-2,4,8-trienoate isopropyl 3,6,8,9-tetramethyldeca-2,4,8-trienoate isopropyl 3,7,9,lO-tetramethylundeca-Z,4,9-

trienoate isopropyl 3 ,6,9, 1 O-tetramethyIundeca ZA,9-

trienoate isopropyl 3,7,12-trimethyltrideca-2,4,l l-trienoate isopropyl 3,7,13trimethyltetradeca-2,4,12-trienoate The reaction of the aldehydes under col. XIV with the carbanion of diethyl 3-methoxycarbonyl-2- methylprop-2-enylphosphonate yields the respective methyl tri-unsaturated esters. [n the same way the respective ethyl tri-unsaturated esters are prepared using diethyl 3-ethoxy-carbonyl-2-methylprop-2- enylphosphonate.

Hydrochlorinated derivatives of the above esters are prepared using the procedure of Example 14 or 39. For example,

isopropyl l l-ch1oro-3,7, 10,1 l-tetramethyldodeca- 2,4-dienoate, isopropyl 1 1-chloro-3,7,10,1 l-tetramethyltrideca- 2,4-dienoate,

isopropyl 10-chloro-3,7,9,10-tetramethylundeca-2,4-

dienoate, and

isopropyl l2-chloro-3 ,7, l2-trimethyltrideca-2,4-

dienoate.

Following the procedure of Example 23 or 29, methanol is added to the terminal double bond of each of the esters under col. XV to prepare:

isopropyl 1 l-methoxy-3,7, 10,1 l-tetramethyldodeca- 2,4-dienoate,

isopropyl l lmethoxy-3,7,10,1 l-tetramethyltrideca 2,4-dienoate,

isopropyl 9-methoxy-3 ,6,9-trimethyldeca-2,4-

dienoate,

isopropyl 9-methoxy-3,6,8,9-tetramethyldecan-2,4-

dienoate,

isopropyl lO-methoxy-3,7,9, l O-tetramethylundeca- 2,4-dienoate,

isopropyl 10-methoxy-3,6,9, 1 O-tetramethylundeca- 2,4-dienoate,

isopropyl 12-methoxy-3,7,12-trimethyltrideca-2,4-

dienoate, and

isopropyl l3-methoxy-3,7,l 3 trimethyltetradeca-2,4-

dienoatev In the same way, ethanol is added to the terminal double bond to prepare the respective ethoxy substituted 2.4-dienoates. Using the procedure of Example 20, water is added to the terminal double bond to prepare the respective hydroxy-substituted 2,4-dienoate.

EXAMPLE 42 A. Eighty ml. of a 3M solution of methylmagnesium bromide in ether is added slowly to 3l g. of citronellal in 250 ml. of dry ether. The mixture is heated at reflux for about 1 hour, cooled to and treated with saturated aqueous ammonium chloride until reaction subsides. The organic layer is separated and the aqueous layer extracted with ether. The organic layer and ether extracts are combined, washed with water and brine and dried over magnesium sulfate. Evaporation of the solvent gives 4,8-dimethylnon-7-en-2-ol.

B. A solution of 47 g. of 4,8-dimethylnon-7-en-2-ol in 250 ml. of methylene chloride is cooled to about lO as a solution of 46.4 g. of sodium dichromate in 125 ml. of water is added. The mixture is maintained at about as a solution of 46.3 g. of sulfuric acid in 100 ml. of water is added over about 45 minutes. The mixture is allowed to attain room temperature and, after about 3 hours, the organic layer is separated and the aqueous layer is extracted with methylene chloride. The combined organic materials are washed with saturated po tassium bicarbonate, water and saturated sodium chloride, dried over magnesium sulfate and evaporated to yield 4,8-dimethylnon-7-en-2-one.

The Grignard reaction of part A is repeated using each 3,7-dimethylnon-6-en-l-al, 3-methyl-7-ethylnon- 6-en- 1 -al, 3 ,6,7-trimethyloct-6-enl -al, 3,7,84rimethylnon-7-enl -al, 2,4,5-trimethylhex-4-enl-al, 2,5-dimethylhex-4-en-l-al, 3,5,6-trimethylhept-5- en-l-a], 3,6-dimethylhept-5-en-l-al, 2,6 -dimethylhept- 5-en-l-al and 2,5,G-trimethylhept-S-en-l-al in place of citronellal to yield the respective secondary alcohol:

4,8-dimethyldec-7-en-2-ol 4-methyl-8-ethyldec-7-en-2-ol 4,7,8-trimethylnon-7-en-2-ol 4,8,9-trimethyldec-8-en-2-ol 3,5,6-trimethylhept 5-en-2-ol 3,6-dimethylhept-5-en-2-ol 4,6,7-trimethyloct6-en-2-ol 4,7-dimethyloct-6-en-2-ol 3,7-dimethyloct-6-en-2-ol 3,6,7-trimethyloct-6-en-2-01 Each of the above alcohols is oxidized to prepare the respective ketone:

4,8-dimethyldec-7-en-2-one 4-methyl-8-ethyldec-7-en-2-one 4,7,8-trimethylnon-7-en-2-one 4,8,9-trimethyldec8-en-2-one 3,5,6-trimethylhept-5-en-2-one 3,6-dimethylhept-5-en-2-one 4,6,7-trimethyloct-6-en-2-one 4,7-dimethyloct-6en-2-one 3,7-dimethyloct-6-en-2-one 3,6,7-trimethyloct-6-en-2-one C. Each of the ketones of part B is reacted with the carbanion of diethyl 3-ethoxycarbonyl-2-methylprop- 2-enyl phosphonate according to procedures described above to prepare the respective tri-unsaturated ester,

ethyl 3.5,7,l l-tetramethyldodeca-2 ,4, l O-trienoatc ethyl 3,5,7,l l-tetramethyltrideca-2,4. l O-trienoate ethyl 3,5 ,7-trimethyl-l l-ethyltrideca-2,4, l0-

trienoate 5 ethyl 3,5,7,l0,l l-pentamethyldodeca-2,4,l0-

trienoate ethyl 3,5,7,l 1,1 2-pentamethyltrideca2,4,l l-

trienoate ethyl 3,5,6,8,9-pentamethyldeca-2,4,8-trienoate ethyl 3,5,6,9-tetramethyldeca-2,4,8-trienoate ethyl 3,5 ,7,9, l O-pentamethylundeca-2,4,9-trienoate ethyl 3,5,7, lO-tetramethylundecal,4,9-trienoate ethyl 3,5,6,lO-tetramethylundeca-2,4.9-trienoate ethyl 3,5,6,9,lO-pentamethylundeca2 4,9 trienoate EXAMPLE 43 A. Each of the ketones of part B of Example 42 is reacted with the carbanion of diethyl 3-ethoxyearbonyll,2-dimethylprop-2-enylphosphonate to prepare the respective trienoate, i.e.,

ethyl 3,4,5.7,l l-pentamethyldodeea-2,4,l0-

trienoate ethyl 3,4,5 ,7,l l-pentamethyltrideca-2,4, l O-trienoate ethyl 3,4,5 ,7-tetramethyl-l l-ethyltrideca-2,4, l O- trienoate ethyl trienoate ethyl trienoate ethyl 3,4,5,6,8,9-hexamethyldeca-2,4,8-trienoate ethyl 3,4,5,6,9-pentamethyldeca-2,4,8-trienoate ethyl 3,4,5,7,9,lO-hexamethylundeca-Z,4,9-trienoate ethyl 3 ,4,5 ,7, l O-pentamethylundeca-Z,4,9-trienoate ethyl 3,4,5,6, lO-pentamethylundeca-2,4,9-trienoate ethyl 3 ,4,5,6,9, l O-hexamethylundeca-Z,4,9-trienoate B. Each of the aldehydes under col. l is reacted with the carbanion of diethyl 3-ethoxycarbonyl-l ,2-dimethylprop-2-enyl phosphonate to prepare the respective 4O trienoate, i.e.,

ethyl 3,4,7,l l-tetramethyltrideca-2,4, lO-trienoate ethyl 3,4,1 l-trimethyl-7-ethyltrideca-2,4, l 0- trienoate ethyl trienoate ethyl 3,4,8,l 2-tetramethyltrideca-2,4,l l-trienoate ethyl 3,4,7,lO-tetramethylundeca-2,4,9-trienoate ethyl 3 ,4,7, l O-tetramethyldodeca-Z,4,9-trienoate ethyl 3,4,6,lO-tetramethylundeca-2,4,9-trienoate By use of the procedure of part B of this example, other aldehydes of formula I (R is hydrogen are converted into the respective ester of formula B wherein R is hydrogen and R is methyl or other lower alkyl. Similarly following the procedure of part A of this example, other ketones of formula I (R is lower alkyl) are converted into esters of formula B wherein each of R and R is lower alkyl. Using the process of part C of Example 42 other esters of the present invention of formula B wherein R is hydrogen and R is methyl of other lower alkyl can be prepared using a ketone of formula l (R is lower alkyl) as the precursor.

C. Each of the esters of this example and Example 42 can be hydrolyzed to the free acid according to the pro 6 cedure of Example 3 or 33. The acid or acid chloride can be reacted with an alcohol such as isopropanol, t-

butanol, benzyl alcohol, and the like to prepare the other esters of the present invention.

3,4,5,7,l0-1 l-hexamethyldodeca-2.4, l 0- 3,4,5,7,l l,l2-hexamethyltrideca-2,4,l l-

3,4-dimethyl-7,l l-diethyltrideca'2 4,lO-

EXAMPLE 44 Following the process of Example 35, ll-methoxy- 3,7,]ltrimethyldodeca-Z.4-dienoic acid is esterified using each of cyclohexanol, n-propanol, i-butanol, benzyl alcohol. phenol n-hexanol, 3,3-dimethyIpentan-lol, 2-methylpentan-l-ol, hexan-2-ol, 3-methylpentanl-ol, p-ethylphenol, a-phenylethanol, Z-fluoroethanol, 2,2-dichloroethanol, 2-chloropropan- 1 ol, 2,2,2- trichloroethanol and and p-methylthiophenol to prepare the respective ester:

cyclohexyl l l-methoxy-3,7,l l-trimethyldodeca-2,4-

dienoate n-propyl l l-methxy-3,7.l ltrimethyldodeca-2,4-

dienoate i-butyl 1 l-methoxy-3,7,l l-trimethyldodeca-2,4-

dienoate benzyl l l-methoxy'3,7,l l-trimethyldodeca-2,4-

dienoate phenyl l l-methoxy-3,7,l l-trimethyldodeca-2,4-

dienoate n-hexyl l l-methoxy-3 ,7,l l-trimethyldodeca-2 ,4-

dienoate l l-methoxy-3 ,7,l l-trimethyl- 1]-methoxy-3,7,l l-trimethyll l-meth0xy-3,7,1 l-trimethyldodecal l -methoxy-3,7,l l-trimethyldodecal l-methoxy-3,7,l l-trimethyll l-methoxy-3,7,l l-trimethyll l-methoxy-3 ,7,l l-trimethyl- EXAMPLE 45 To a solution of 0.5 g. of trans, trans ll-methoxy- 3,7,1ltrimethyldodeca-Z,4-dienoic acid in ml. of benzene is added, with stirring, an equivalent amount of potassium hydride. The mixture is stirred at room temperature for about 2 hours and then evaporated to give potassium ll-methoxy-3,7,lltrimethyldodeca- 2,4-dienoate.

In place of KH, there can be used KOH, NaOH, and the like to form the corresponding salt.

EXAMPLE 46 Methanol is added to the terminal bond of ethyl 3,4,- 7,1 l tetramethyldodeca-LZA, l O-trienoate using the process of Example 23 or 29 to give ethyl l l-methoxy- 347.1 ltetramethyldodeca-Z,4-dienoate. In the same manner, water is added to give ethyl l l-hydroxy- 3,4,7,l ltetramethyldodeca-2,4-dienoate. Similarly. there is prepared ethyl l l-methoxy-3,5,7,l ltetramethyldodeca-Z,4-dienoate and ethyl l lhydroxy- 3,5,7,l ltetramethyldodeca-2,4-dienoate from ethyl 3,5,7,l l-tetramethyldodeca-2,4,lO-trienoate. The hydrochloride, ethyl l l-chloro-3,4,7,l l-tetramethyldodeca-2,4-dienoate and ethyl ll-chloro-3,5,7,l ltetramethyldodeca-2,4-dienoate are prepared from the trienoate using the process of Example 39.

EXAMPLE 47 A. To a solution of 1.8 g. of 6,lO-dimethylundeca- 3,9-dien-2-one in 20 ml. of ethanol, cooled to 0 by an ice bath is added a suspension of 2.32 g. of mercuric acetate in 50 ml. of ethanol over 15 minutes. The reaction mixture is stirred for 2 hours and then, with cooling, to 20, 1.22 g. of potassium hydroxide in 20 ml. of ethanol is added. Then 0. l 39 g. of sodium borohydride is added in small portions and stirring continued for 30 minutes at 20. The solution is decanted, then concentrated to half volume, diluted with ml. of water and extracted with ether (3 X 50). The ethereal phase is washed with water, dried over magnesium sulfate and the crude product chromatographed on silica to yield 10-ethoxy-6, l O-dimethylundec-Ii-en-2-one.

The process of this example is repeated using each of the compounds under column VI as the starting material to prepare the respective ethoxy substituted compound under column XVI.

l0-ethoxy-6,lO-dimethyldodec-3-en-2-one lO-ethoxy-fi-methyll 0-ethyldodec-3-en-2-one l O-ethoxy-6, l O-diethyldodec-3-en-2-one l l-ethoxy-7,l ldimethyldodec3-en-2-one 9-ethoxy-6,9-dimethyldec-3-en-2-one 9-ethoxy-6,9-dimethylundec-3-en-2-one 9-ethoxy-5,9-dimethyldec-3en-2-one Following the process of Example 13, lO-ethoxy- 6, lO-dimethylundec-3en-2-one is converted into methyl 1 l-ethoxy-3,7,1 ltrimethyldodeca-2,4 dienoate. Reaction of lO ethoxy-,lO-dimethylundec- 3-en-2-one with the carbanion of diethyl carboethoxymethylphosphonate yields ethyl 11- ethoxy-3 ,7,l ltrimethyldodeca-2,4-dienoate.

By using other alcohols in the process of this example in lieu of ethanol, such as methanol, etc., the respective ethers are obtained, e.g. lO-methoxy-6,lO-dimethylundec-3-en-2-one.

B. The process of part A is repeated using the starting material 3,7-dimethyloct-6-en-l-al and each of the aldehydes under column I or the acetal thereof to prepare the respective compounds under column XVII.

XVll

7-ethoxy3,7-dimethyloctan 1 al 7-ethoxy-3,7-dimethylnonanl a] 7-ethoxy-3ethyl-7-methylnonan-1al 7-ethoxy-3 ,ldiethylnonan- 1 al 8'ethoxy4,8 dimethylnonan- 1 al 6-ethoxy-3 ,fi-dimethylheptan- 1 al 6-ethoxy-3 ,fi-dimethyloctan- 1 al 6-ethoxyQb-dimethylheptanal Using 7-ethoxy-3,7-dimethyloctanl al as the starting material in the process of either Example 9, 10 or i 1, there is prepared l0-ethoxy-6,l0-dimethylundec-3-en- 2-one.

EXAMPLE 48 A mixture of 0.6 g. of l lmethoxy-3,7,l l-trimethyldodeca-ZA-dienoic acid (mostly trans, trans), l0 ml. of

dry benzene and 0.21 ml. of oxalyl chloride is allowed to stand at room temperature with occasional stirring for about 2.5 hours. The mixture is cooled in cold water and then 0.18 ml. of ethylmercaptan added. The reaction is stirred and drops of dry pyridine added. The reaction is stirred at room temperature for 2 hours and then worked up by addition of ether and saturated sodium bicarbonate, washing of organic phase and removal of solvent to yield crude ethyl 1 l-methoxy- 3 ,7,1 l-trimethyl-thioldodeca-2,4-dienoate (mostly trans, trans) which is separated by preparative thin layer chromatography.

EXAMPLE 49 To 0.55 g. of 1 1-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienoic acid in 10 ml. of dry benzene is added 0.21 ml. of oxalyl chloride. The mixture is stirred occasionally at room temperature for about 2.5 hours. The mixture is cooled in cold water and then 0.18 ml. of ethylmercaptan is added with stirring. The mixture is then stirred at room temperature for about 24 hours. Ether and saturated sodium bicarbonate is added and the organic phase separated. The organic phase is washed with aqueous sodium bicarbonate, saturated sodium chloride, dried over calcium sulfate and evaporated to yield ethyl 11-methoxy-3,7,l l-trimethyl-thioldodeca- 2,4-dienoate.

Thiol esters are prepared using each of n-propyl mercaptan isopropyl mercaptan, isobutyl mercaptan, sbutyl mercaptan, n-butyl mercaptan, benzyl mercaptan, cyclopentyl mercaptan,B-phenylethyl mercaptan, t-amyl mercaptan and n-hexyl mercaptan in reaction with 1 l-methoxy-3,7,l l-trimethyldodeca-2,4-dienoyl chloride or the sodium salt of l l-methoxy-3,7,1 1- trimethyldodeca-2,4-dienoic acid to yield n-propyl 1 1-methoxy-3,7,l l-trimethyl-thioldodeca- 2,4-dienoate isopropyl 1 l-methoxy-3,7,l l-trimethyl-thioldodeca- 2,4-dienoate isobutyl 1 1 methoxy-3,7,l l-trimethyl-thioldodeca- 2,4-dienoate s-butyl 1 l-methoxy-3,7,1 1 -trimethyl-thioldodeca- 2,4-dienoate n-butyl 1 1-methoxy-3,7,1 l-trimethyl-thioldodeca- 2,4-dienoate benzyl l 1-methoxy-3,7,1 l-trimethyl-thioldodeca- 2,4-dienoate cyclopentyl 1 1-methoxy-3,7,1 l -trimethy1thiolmethoxy'3,7,1 1-trimethylthioldodeca2,4-dienoic acid.

Thiol acids serve as precursors for the preparation of other thiol esters of the present invention.

EXAMPLE 50 To a solution of 25.4 g. of 3,7,11-trimethy1dodeca- 2,4,10-trienoyl chloride is ether is added 12.4 g. of ethylmercaptan and 11.6 g. of pyridine at 40. The mixture is allowed to stand at 0 for about 3 hours and then diluted with ether and water and separated. The ether phase is washed with dilute aqueous sodium hydroxide, dilute hydrochloric acid and then water, dried and solvent removed to yield ethyl 3,7,1 l-trimethylthio1dodeca-2,4, IO-trienoate.

The process of this example or Example 49 is repeated using each of the acid chlorides under column XVIII to prepare the respective thiol ester under column XlX.

XVlll chlochlochlo- XIX ethyl 3,7,1 1 trimethyl-thioltrideca-Z,4, IO-trienoate ethyl 3,1 1-dimethyl-7-ethyl-thioltrideca-2,4, l O- trienoate ethyl 7,1 1-diethyl-3-methyl-thioltrideca-2,4, l 0- trienoate ethyl 3,7, lO-trimethyl-thiolundeca-2,4,9-trienoate ethyl 3,7,10-trimethyl-thioldodeca-2,4,9-trienoate ethyl 3,6,lO-trimethyl-thiolundeca-2,4,9-trienoate ethyl 3,7, 10,1 l-tetramethyl-thioldodeca-2,4,10-

trienoate ethyl 3,5 ,7,1 1-tetramethy1-thioldodeca-2,4, l 0- trienoate ethyl 3,4,7,1 l-tetramethyl-thioldodeca-2,4, l0-

trienoate ethyl 3,5 ,7, 10,1 l-pentamethyl-thioldodeca-2,4,10-

trienoate Methylmercaptan is reacted with each of the trienoylchlorides above using the procedure of this example or Example 49 except that the reaction mixture is prepared at about 10 and the reaction is carried out in a sealed vessel to prepare the respective methyl thiol esters, e.g., methyl 3,7,1 l-trimethyl-thioltrideca- 2,4,l0-trienoate. methyl 3,7,10-trimethyl-thioldodeca- 2,4,9-trienoate, etc.

EXAMPLE 51 3,7,11-trimethyltrideca2,4,IO-trienoyl chloride (18 g.) is added slowly to ethyl lead mercaptide (13.4 g.) covered with ether. The mixture is allowed to stand overnight and then is filtered. The filtrate is evaporated under reduced pressure to yield ethyl 3,7,1 l-trimethylthioltrideca-2,4,IO-trienoate which can be purified by chromatography.

EXAMPLE 52 Fifteen grams of mercuric acetate in 50 ml. of dry ethanol is added to 12 g. ofethyl 3,7,1 l-trimethyl-thioldodeca-2,4, IO-trienoate in 30 ml. ofdry ethanol cooled in an ice bath. The temperature is allowed to come to room temperature by standing overnight. Then the mixture is cooled to g. of potassium hydroxide in 150 ml. of ethanol is added followed by addition of l .0 g. of sodium borohydride in small portions. After about 30 minutes at 0, water is added and mixture left at room temperature for 2 hours. The mixture is filtered, filtrate concentrated and extracted with ether. The ethereal extract is washed, dried and evaporated to yield ethyl l l-ethoxy-3,7,1 l-trimethylthioldodeca-2,4- dienoate which is purified by chromatography.

By using methanol in the foregoing process in place of ethanol, there is prepared the respective ll methyl ether.

Using each of the esters under column XIX as the starting material in the process of this example, there is prepared the respective substituted ester under column XX.

ethyl l 1-ethoxy-3,7,l l-trimethyl-thioltrideca-2,4-

dienoate ethyl 1 l-ethoxy-3,1 l-dimethyl-7-ethyl-thioltrideca- 2,4-dienoate ethyl l 1-ethoxy-7,l l-diethyl-3-methyl-thioltrideca- 2,4-dienoatc ethyl 10-ethoxy-3,7, l O-trimethyl-thiolundeca2,4-

dienoate ethyl 10-ethoxy-3 ,7, l O-trimethyl-thioldodeca-2,4-

dienoate ethyl l0-ethoxy-3,6, l O trimethyl-thiolundeca-2,4-

dienoate ethyl l l-ethoxy-3,7,10,1 l-tetramethyl-thioldodeca- 2,4-dienoate ethyl l l-ethoxy-3 ,5 ,7,1 l-tetramethyl-thioldodeca- 2,4-dienoate ethyl l l-ethoxy-3,4,7,l l-tetramethyl-thio1dodeca 2,4-dienoate ethyl 1 1-ethoxy-3,5,7,10,l l-pentamethyl-thioldodecaQA-dienoate EXAMPLE 53 To a mixture of 1,9 g. of mercuric acetate, 6 ml. of water and ml. of tetrahydrofuran is added 1.49 g. of ethyl 3,7,1 l-trimethyl-thioldodeca-2,4, l O-trienoate slowly. After addition is complete, the reaction mixture is stirred for about 20 minutes. The mixture is cooled to about 0 and 6 ml. of aqueous sodium hydroxide (3 molar) is added followed by 0.49 g. of sodium borohydride in aqueous sodium hydroxide (about 3 molar). The mixture is stirred for about 30 minutes. The mixture is then decanted, concentrated, diluted with water and then extracted with ether. The ethereal extract is washed with water, dried over magnesium sulfate and the product chromatographed to yield ethyl l lhydroxy-3,7,1 ltrimethyl-thioldodeca-2,4-dienoate.

The above process is repeated using each of the unsaturated esters under column XIX to prepare the respective compound under column XXI.

ethyl l l-hydroxy3,7,l 1-trimethyl-thioltrideca-2,4-

dienoate ethyl l l-hydroxy-3,l ldimethyl7-ethyl-thioltrideca- 2,4-dienoate ethyl l l-hydroxy-7,l l-diethyl-3-methyl-thioltrideca- 2,4-dienoate ethyl l0-hydroxy-3,7,10-trimethyl-thiolundeca-2,4-

dienoate ethyl l0-hydroxy-3 ,7, l 0-trimethyl-thioldodeca-2,4-

dienoate ethyl l0-hydroxy-3 ,6, l O-trimethyl-thiolundeca-2,4-

dienoate ethyl l -hydroxy-3,7,1 0,1 1-tetramethy1-thioldodeca- 2,4-dienoate ethyl 1 1-hydroxy-3,5,7,l l-tetramethyl-tliioldodeca- 2,4-dienoate ethyl 1 1-hydroxy-3 ,4,7 ,1 1-tetramethyl-thioldodeca- 2,4-dienoate ethyl 1 l-hydroxy-3 ,5,7, 10,1 l-pentamethyl-thioldodeca-2,4-dienoate.

Following the procedure of Example 24 or 25, each of the above hydroxy substituted thiol esters is converted into the respective carboxylic acyloxy, e.g. acetoxy, substituted thiol esters. For example, ethyl 11- acet0xy3,7, 1 1-trimethyl-thioldodeca-2,4-dienoate. Similarly, formates can be prepared from the thioltrienoates or hydroxysubstituted thiol-dienoates.

One gram of ethyl 1 l-hydroxy3,7,1 l-trimethyl-thioldodeca-2,4-dienoate in 10 m1. of digylme is added dropwise to a slurry of 1 g. of sodium hydride in 10 ml. of diglyme under nitrogen. To this mixture is added 0.9 of cyclohexylchloride. The reaction mixture is stirred at about 25 for 30 minutes and then quenched in ice water. The organic phase is separated and aqueous phase re-extracted with ether. The organic materials are washed with water, dried over sodium sulfate and evaporated to yield the cyclohexyl ether of ethyl 11- hydroxy-3 ,7,1 1-trimethy1-thioldodeca-2,4-dienoate.

By using each of benzyl chloride and cyclopentyl chloride in the foregoing procedure, the corresponding benzyl ether and cyclopentyl ether is prepared.

By use of the procedure of Example 25, ethyl 11- hydroxy-3 ,7,1 1-trimethylthioldodeca-2,4-dienote is converted into the corresponding 1 l-chloroacetate, ll-dichloracetate and ll-trichloroacetate using chloracetyl chloride, dichloroacetyl chloride and trichloroacetyl chloride, respectively.

The respective l l-triflouracetate, propionate, nbutanoate, n-pentanoate and n-hexanoate esters of ethyl l 1-hydroxy-3,7,l 1-trimethyl-thioldodeca-2,4- dienoate are prepared according to the process of Example 24 using trifluoracetic anhydride, propionic anhydride, n-butyric anhydride, n-pentanoic anhydride and n-hexanoic anhydride or according to the process of Example 25 using the corresponding acid chloride.

Following the process of Example 53, each of npropyl l l-hydroxy3,7,l 1-trimethyl-thioldodeca-2,4- dienoate, isopropyl l1-hydroxy-3,7,1l-trimethyl-thioldodeca-2,4-dienoate, isobutyl l lhydroxy-3,7,l ltrimethy1-thio1dodeca-2,4-dienoate, s-butyl 1 lhydroxy-3 ,7 ,1 1-trimethyl-thioldodeca-2,4-dien0ate, t-butyl l l-hydroxy-3,7,1 l-trimethyl-thioldodeca-2,4- dienoate, benzyl l l-hydroxy-3,7,l l-trimethyl-thioldodecaJA-dienoate, cyclopentyl 1 1-hydroxy-3,7,l 1- trimethyl-thioldodeca-2,4-dienoate, t-amyl 1 1- hydroxy-3 ,7,1 1-trimethyl-thioldodeca-2,4-dienoate, B-phenylethy] 1 l-hydroxy-3,7,1 l-trimethyl-thioldodeca-2,4-dienoate, and n-hexyl l1-hydroxy-3,7,l1- trimethyl-thioldodeca-2,4-dienoate is prepared from the respective 2,4,lO-tri-unsaturated thiolester.

Each of the l l-hydroxy-2,4-diunsaturated thiolester is esterified using the process of Example 24 or 25 to prepare the respective l l-acetate, that is, n-propyl l 1 acetoxy-3 ,7,1 1-trimethyl-thioldodeca-2,4-dienoate, isopropyl l l-acetoxy-3,7,l l-trimethyl-thioldodeca- 2,4-dienoate, etc.

EXAMPLE 5 4 A. Anhydrous hydrogen chloride is bubbled into 100 ml. of dry carbon tetrachloride at 0 until one equivalent is taken up. Five grams of ethyl 3,7,1 1- trimethylthioldodeca-2,4,10-trienoate is added and the resulting mixture allowed to stand for about 48 hours at 20. The mixture is evaporated under reduced pressure to yield ethyl 1 l-chloro-3,7,1 l-trimethylthioldodeca-2,4-dienoate, which is purified by chromatog raphy.

The above process or the process of Example 39 is repeated using each of the unsaturated compounds under Column XIX to prepare the respective chloride under Column XXII.

XXII

ethyl 1 1-chloro-3 ,7,1 l-trimethylthioltrideca-2,4-

dienoate, ethyl l l-chloro-3,l l-dimethyl-7-ethylthioltrideea- 2,4-dienoate, ethyl 1 l-chloro-7,l l diethyl-3-methylthioltrideca 2,4-dienoate,

ethyl l0-chloro-3 ,7 ,10-trimethylthiolundeca-Z,4-

dienoate,

ethyl 10-chloro-3 ,7,10-trimethylthioldodeca-Z,4-

dienoate,

ethyl 10-chloro-3 ,6,10trimethylthiolundeca-2,4-

dienoate,

ethyl l 1-chloro-3,7,10,1 l-tetramethylthioldodeca 2,4-dienoate,

ethyl l 1 -chloro-3 ,5 ,7, l l-tetramethylthioldodeca- 2,4-dien0ate,

ethyl l 1-chlor0-3,4,7,1 l-tetramethylthioldodeca- 2,4-dienoate,

ethyl l 1-chloro-3,S,7,l0,l l-pentamethylthioldodeca-2,4-dienoate.

By using each of hydrogen bromide and hydrogen fluoride in the above process, the respective bromides and fluorides are prepared, e.g., ethyl ll-bromo- 3,7,1 1-trimethylthioldodeca-2,4-dienoate, ethyl I lfluoro-3,7,l l-trimethylthioldodeca-2,4-dienoate, etc.

B. Chlorine gas is bubbled into 200 ml. of carbon tetrachloride at 0 until one equivalent is taken up. Twenty-five grams of ethyl 3,7,1 l-trimethylthiol dodeca-2,4,10-trienoate is added and the mixture stirred and then allowed to stand at about 20 for 24 hours. The mixture is then evaporated to yield ethyl 10- ,l l-dichloro-3,7,1 1-trimethylthioldodeea-2,4- dienoate, which can be purified by chromatography.

By repeating the above process using each of the triunsaturated esters under Column XIX, the respective dichloro dienoates are prepared, i.e., ethyl 10,1 1- dichloro-3,7,1 1-trimethylthioltrideca-2,4-dienoate, ethyl 10,1 l-dichloro-3,1 1-dimethyl-7-ethylthioltrideca-2,4-dienoate, etc.

By using bromine in place of chlorine in the foregoing process, the respective dibromo derivatives are prepared, i.e., ethyl 10,1 l-dibromo-3,7,l l-trimethylthioldodeca-2,4-dienoate, etc.

C. To a mixture of 5 g. of ethyl 3,7,1 l-trimethylthioldodeca-2,4,l0-trienoate in 100 ml. of fluorotrichloromethane, is slowly added one equivalent of anhydrous fluorine at about -78. After stirring the mixture at this temperature for about 16 hours, the resultant mixture is evaporated and chromatographed on silica to yield ethyl 10,1 l-difluoro3,7,l l-trimethylthioldodeca-2,4-dienoater By repeating the above process using the triunsaturated esters under Column XIX, the respective difluoro dienoates are prepared, i.e., ethyl 10,1 1- difluoro-3,7,l 1-trimethylthio1trideca-2,4-dienoate, etc.

EXAMPLE 55 A mixture of 3.0 g. of sodium acetate and 20 ml. of acetic anhydride is stirred at room temperature for 0.5 hour. To the mixture is added 2.7 g. of isopropyl llhydroxy-3 ,7,l 1-trimethyldodeca-2,4-dienoate. The mixture is warmed up to 100 and left overnight (about 17 hours). After cooling, the mixture is poured into sat. sodium bicarbonate and extracted with ether. The combined ether extracts are washed with aqueous sodium bicarbonate, water and sat. sodium chloride solution, dried over calcium sulfate and concentrated to give crude isopropyl 1 l-acetoxy-3,7,l l-trimethyldodeca-2,4-dienoate which is filtered through Florisil using 5% ethyl acetate/hexane and then distilled for purification.

By using ethyl 11-hydroxy-3,7,11trimethyldodeca- 2,4-dienoate in the above procedure, there is prepared ethyl l l-acetoxy-3,7,l 1-trimethyldodeca2,4-dienoate.

EXAMPLE 56 To a solution of 2.0 g. of ethyl 3,7,1 l-trimethyldodeca-2,4,10-trienoate in 30 m1. of ethanol, cooled in an ice bath, is slowly added 5.24 g. of acetyl chloride. The reaction mixture is allowed to rise to room temperature and stirred for about 60 hours. The mixture is concentrated under reduced pressure and the concentrate poured into water/hexane. The organic layer is separated, washed with aqueous sodium bicarbonate, water and brine, dried over calcium sulfate and solvent removed to yield ethyl l l-chloro-3,7,l l-trimethyldodeca-2,4-dienoate.

EXAMPLE 57 To an ice cold solution of 2.0 g. of isopropyl 3,7,] 1- trimethyldodeca-2,4, lO-trienoate in 80 ml. of isopropa no] is added 2.29 g. of mercuric acetate over about 15 minutes. The mixture is stirred at ice temperature for 3 hours and then at room temperature for about 17 hours. A solution of 1.21 g. of potassium hydroxide, 5 ml. of water and 20 ml. of isopropanol is then added to the mixture cooled in an ice bath. Then 0.126 g. of sodium borohydride is added in small portions and stirring continuted for 1 hour. The mixture is then stirred with Celite and mercury filtered off. The filtrate is concentrated under reduced pressure, diluted with water and extraced with ether. The combined ether extracts are washed with water and brine, dried over calcium sulfate and solvent removed to give isopropyl 11- isopropoxy-3,7,1 l-trimethyldodeca-2,4-dienoate 35 which can be purified by chromatography or distillation.

EXAMPLE 58 To a solution of 40 g. of 7-hydroxy-3,7- dimethyloctan-l-al in 100 ml. of dimethylformamidc, cooled to and under nitrogen, is added 71.2 g. of di isopropyl 3-isopropoxycarbonyl-2-methylprop-Zenyl phosphonate in 100 ml. of dimethylformamide through a dropping funnel. The mixture is stirred at 0 for 0.5 hour and then 9.3 g. of ground sodium hydroxide is added. The reaction mixture is stirred at room temperature for about 3 hours and then poured into hexane/- water (1:1). The aqueous layer is extracted with hexane. The hexane extract is combined with the organic layer which is washed with water and brine, dried over calcium sulfate and solvent removed to yield isopropyl l 1-hydroxy-3 .7,i l-trimethyldodeca-2,4-dienoate.

EXAMPLE 59 To a solution of 6.0 g. of ll-methoxy-3,7.l1-trimethyldodeca-2,4-dienoic acid and 125 ml. of dry benzene in a water bath is added 6 ml. of oxalyl chloride. After 1.5 hours, the mixture is heated at 60 to 0.5 hour. Then solvent is removed under reduced pressure. To the residue is added 125 ml. of dry benzene and ml. of isopropyl mercaptan. The mixture is stirred for 2 hours and then refluxed gently (bath 70) for 17 hours. After cooling, the mixture is poured into water and diluted with ether. The organic phase is separated and washed with aqueous sodium bicarbonate and brine, dried over calcium sulfate and evaporated under reduced pressure to give isopropyl l l-methoxy-3.7,l 1- trimethylthioldodeca-2,4-dienoate.

By using ethyl mercaptan in the process of this exam ple in place of isopropyl mercaptan, there is prepared ethyl 1 l-methoxy-3 .7,1 l-trimethylthioldodeca-Z ,4- dienoate.

EXAMPLE 60 EXAMPLE 61 ll-methoxy-3,7,l

Following the procedure of Example 35, each of sec-butyl alcohol and sec-butyl alcohol is reacted with the acid chloride of trans. trans l l-methoxy- 3,7,1 l-trimethy1dodeca-2,4-dienoic acid to prepare sec=butyl l 1-methoxy-3,7,l l-trimethyldodeca- 2(trans), 4(trans)-dienoate and sec. butyl l l methoxy 3,7,1 l-trimethyldodeca-2(trans), 4(trans)- dienoate.

Each of penta-2,3'-dienyl ll-methoxy-3,7,l 1- trimethyldodeca-Z,4-dienoate, pent-2'-yn-1"yl l 1- methoxy-3,7,l 1trimethyldodeca-2,4-dienoate and but-3 '-enl -yl 1 1-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienoate is prepared using penta-2.3-dien-1-ol, pent-Z-yn-l-ol and but-3en-1-ol in the process of Example 35 in place of isopropanol.

EXAMPLE 62 To a solution of 4.15 g. of l l-methoxy-3,7,1 l-trimethyldodeca-2,4-dienoic acid in 100 ml. of dry benzene, under nitrogen, is added 5.1 ml. of oxalyl chloride. After 2 hours, solvent is removed under reduced pressure and 100 ml. of fresh dry benzene and 6.4 ml. of dry isobutyl alcohol is added. The reaction mixture is concentrated and the concentrate is stirred over 20 g. of activated alumina in pentane for 0.5 hr. and filtered. The filtrate is washed, dried and evaporated under reduced pressure to give isobutyl 1 1-methoxy-3,7,l 1- trimethyldodeca-Z,4-dienoate which can be purified by distillation.

EXAMPLE 63 A solution of 20 g. of potassium hydroxide granules in 80 ml. of ethanol is prepared and then hydrogen sulfide is passed into the solution with stirring and cooling until the solution is saturated and does not give an alkaline reaction with phenolphthalein. At about 1015, 33.5 g. of 1 1-methoxy-3,7.1 l-trimethyldodeca-2,4-dienoic acid is added dropwise with stirring and maintaining temperature of l0-15. After addition is complete, the reaction mixture is stirred for about one hour. Then the mixture is filtered and the filter washed with ethanol The combined filtrate and washings are evaporated under reduced pressure. Water is added to the concentrate and then extracted with benzene. The aqueous phase is acidified with cold 6N hydrochloric acid and then extracted with ether. The ether extracts are washed with cold water, dried over sodium sulfate and ether evaporated to give crude 1 1-methoxy-3,7,1 1-trimethyl-thioldodeca-2,4-dienoic acid which can be purified by chromatography.

Three groups of 30 each of Aedes aegypti, fourth instar larvae, in 50 ml. of tap water containing a few drops of liver powder suspension, room temperature of 28 and photoperiod of 18 hours. are treated with ethyl l l-methoxy-3,7,l l-trimethyldodeca2,4-dienoate (about 58% trans, trans) using 50 microliters of acetone as the carrier at three different dosage levels. A fourth group is maintained under identical conditions. Each group is scored after seven days by the following system: 0 normal adult. completely emerged (free or floating); l abnormal adult, non-viable; 2 incompletely emerged adult; 3 dead pupa; and 4 =dead larvae. For each group the total number of animals in classes l4 is divided by 30 to determine the percentage result. The ID is computed by plotting on semilogarithmic paper, the dose on the horizontal axis and the percentage response on the vertical axis. THe ID was determined to be less than 1.0 ppm. Each of the larvae of the control group developed into normal adults. Each of the compounds, methyl ll-methoxy- 3,7,1 1-trimethyldodeca-2,4-dienoate (78% trans, trans). ethyl ll-hydroxy-3,7.1l-trimethyldodeca-2,4- dienoate (85% trans, trans), t-butyl l l-methoxy- 3,7,]-

l-trimethyldodeca-2,4-dienoate, 2'-methoxyethyl l 1- methoxy-3,7,l l-trimethyldodeca-2,4-dienoate, 3 thiacyelohexyl 1 1-methoxy-3,7,l l-trimethyldodeca- 2,4-dienoate and 2'-methylthioethyl ll-methoxy- 3,7,1 l-trimethyldodeca-2,4-dienoate were tested in the same way and found to have an lD of less than 1.0 pp

Three groups of 20 each of Tenebrio molitor pupae (less than 24 hours old) maintained on wheat germ and bran, 25 room temperature, 18 hours light, are treated at 0.1, 1.0 and 10.0 pig. with isopropyl ll-methoxy- 3,7,1 l-trimethyldodeca-2,4-dienoate (predominantly all trans) using acetone carrier. The active agent is placed on the 5th abdominal sternite using a syringe. The lD was less than 0.1 pg.

Concentrate suitable for field application, with or without dilution depending upon spraying apparatus can be formulated as follows (percentage by weight).

lsopropyl l 1-methoxy-3,7 ,1 l-

trimethyldodeca-Z,4-dienoate Emcol N'140B, a blend of polyoxyethylene ethers and oilsoluble sulfonates, and Emcol T-l 80, are trade names for surfactants of Witco Chemical New York, New York.

The above concentrate can be applied without dilution using ultralow volume Sprayers or can be diluted with, for example, water before application. Dilution containing the active component within the range of about 0.001% to are generally employed. A dilution of the above concentrate with water to provide 10% of the active component, when applied to locals infested with immature peach aphids, provides efi'eo tive control.

A fine dust is prepared of 10 parts of isopropyl l lmethoxy3,7,11-trimethy1dodeca-2,4-dienoate and 90 parts synthetic fine silica, by weight, by blending in a Waring Blendor. The fine dust is particularly useful for application to broadleaf plants for the control of cabbage looper, turnip aphids and squash vine borer.

[sopropyl 1 1-methoxy-3,7,l 1-trimethyldodeca-2,4- dienoate (56% trans, trans) is put neat on wheat to provide a concentration of 5 ppm and super-blended. The treated wheat is placed in a large glass container and viable adult lndianmeal moths (Plodia imerpunctella) introduced. The same quantity of untreated wheat is placed in a large glass container and 20 viable adult lndian-meal moths introduced. The two groups are maintained under identical conditions for eight weeks. In the case of the treated grain, the 20 adults survived and the grain contained a few larvae and non-viable pupa, the larvae were not active and instead existed in diapause or pre-pupal-like state indicates essentially complete control for protection of the grain. The untreated grain (control) all adults survived and the grain was infested with hundreds of active larvae. The same treatment was made of other stored grain pests i.e., Merchant grain beetle (Oryzaephilus mercator),

Almond moth (Cadra caurella) and Sawtoothed grain beetle (Oryzaephilus suri'namensis) and provided essentially complete control by inhibiting adult emergence.

In some applications of the compounds of the present invention, it is advantageous to formulate the active compound of formula A or B, such as an ester of formula A with a polymeric material or a combination of polymer, filler, plasticizer and stabilizers. Thus, in the use of, e.g., an ester of formula A as a control agent for mosquitos, the active compound can be blended with a polymer, such as polyvinyl chloride, and copolymers of polyvinyl chloride or ethylenepropylenediene terpolymers as described in US. Pat. No. 3.590,1 19 to extend the life and effectiveness for control of mosquito larvae. The density of blended or encapsulated material can be gauged so as to make it available at the most optimum water level. Polymeric blends and encapsulation of the active compounds of the present invention can be usefully applied to provide effective control of insects which harbor in the surface or under the surface of the soil as immature insects. Suitable polymers, blended techniques and encapsulation methods are de scribed in US. Pat. Nos. 2,777,824; 3,005,297; 3,318,769; 3,393,990; 3,499,962; 3,551,556; 3,565,818; 3,565,559; 3,565,819 and 3,577,515.

Although not intending to be limited by a theoretical explanation, the effectiveness of the compounds of the present invention to control insects is attributed to the property of these novel compounds to mimic the activity of juvenile hormone as demonstrated herein. While the methods of applying and carriers for conventional insecticides are usually adaptable to the practical use of the compounds of the present invention, the mechanism of action of these novel compounds is unlike that of conventional insecticides. Whereas conventional insecticides are dependent upon direct knockdown ef' fect, toxity effect or paralyzing effect, the compounds of this invention achieve control by reason of their ability to inhibit metamorphosis, inhibit reproduction due to abnormal development, break diapause at an unfavorable time, or act as a direct insecticide, particularly at the embryo stage and larvae stage. Treatment of insects in accordance with the present invention can be achieved via ingestion of the active compound in the normal food of the insect and by topical application, that is, by contact of the epidermis of the insect as by spraying the insect and habitat of the insect or exposure to vapors of the active compound which penetrate into the insect.

The compounds of the present invention can be used in conjunction with other juvenile hormone active substances and conventional insecticides to obtain a broad spectrum of activity or to provide more immediate effect on very heterogeneous populations. Typical insecticides which may be combined with the compounds of the present invention are Malathion, Sevin, Vapona, Abate, synthetic and natural pyrethrins, and the like, and usually within the ratio of between 10: l to 1: 10, by weight.

The following is an example of a granule formulation in accordance with the present invention:

Attaclay 15-30 Propylene glycol 1% Compound A or B 19% 

1. A COMPOUND SELECTED FROM THOSE OF THE FORMULA:
 2. A compound according to claim 1 of the formula:
 3. A compound according to claim 2 wherein R15 is lower alkyl.
 4. A compound according to claim 2 wherein Z is chloro or the group -OR in which R is hydrogen, methyl, ethyl, isopropyl, t-butyl or acetyl; n is one; R1 is methyl; R14 is hydrogen; and R15 is methyl, ethyl or isopropyl.
 5. A compound according to claim 4 wherein Z is methoxy or ethoxy and each of R2 and R3 is methyl.
 6. A compound according to claim 5 wherein R15 is methyl or ethyl.
 7. A compound according to claim 2 wherein n is one; Z is methoxy or ethoxy; and R15 is lower alkyl of one to four carbon atoms.
 8. The compound, 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoic acid, according to claim
 2. 9. The compound, methyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate.
 10. The compound, ethyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate.
 11. The trans(2), trans(4) isomer of the compound of claim
 10. 12. The compound, isopropyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate.
 13. The compound, n-propyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate.
 14. The compound, ethyl 11-hydroxy-3,7,11-trimethylthioldodeca-2,4-dienoate.
 15. The compound, isopropyl 11-hydroxy-3,7,11-trimethylthioldodeca-2,4-dienoate.
 16. The compound, n-propyl 11-hydroxy-3,7,11-trimethylthioldodeca-2,4-dienoate, according to claim
 2. 17. A compound according to claim 2 wherein Z is chloro; n is one; each of R1, R2 and R3 is methyl; R14 is hydrogen; and R15 is methyl or ethyl.
 18. The compound, ethyl 11-chloro-3,7,11-trimethylthioldodeca-2, 4-dienoate, according to claim
 17. 19. A compound according to claim 2 wherein Z is the group -OR in which R is hydrogen or lower alkyl; each of R1, R2 and R3 is methyl; R14 is hydrogen; and R15 is lower alkenyl, lower alkynyl or cycloalkyl of three to eight carbon atoms.
 20. The compound, allyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate, according to claim
 19. 21. The compound, propargyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate, according to claim
 19. 22. The compound, cyclopropyl 11-methoxy-3,7,11-trimethylthioldodeca-2,4-dienoate, according to claim
 19. 23. A compound selected from those of the formula:
 24. A compound according to claim 23 wherein R15 is lower alkyl of one to four carbon atoms.
 25. A compound according to claim 24 wherein n is one and each of R12 and R13 is hydrogen.
 26. The compound, methyl 3,7,11-trimethylthioldodeca-2,4,10-trienoate, according to claim
 25. 27. The compound, ethyl 3,7,11-trimethylthioldodeca-2,4,10-trienoate, according to claim
 25. 28. The compound, propargyl 3,7,11-trimethylthioldodeca-2,4,10-trienoate, according to claim
 23. 29. The compound, ethyl 11-ethoxy-3,7,11-trimethylthioldodeca-2, 4-dienoate, according to claim
 7. 